Expandable tip assembly for thrombus management

ABSTRACT

Systems, methods, and devices for the treatment of acute ischemic stroke that provide immediate blood flow restoration to a vessel occluded by a clot and, after reestablishing blood flow, address the clot itself. Immediate blood flow restoration advantageously can facilitate natural lysis of the clot and also can reduce or obviate the concern for distal embolization due to fragmentation of the clot. Several embodiments of the invention provide for progressive, or modular, treatment based upon the nature of the clot. For example, the progressive treatment can include immediate restoration of blood flow, in-situ clot management, and/or clot removal depending on the particular circumstances of the treatment. The in-situ clot management can include, for example, lysis, maceration, and/or removal.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/924,703, filed Jun. 24, 2013, which is a continuation of U.S. patentapplication Ser. No. 13/281,363, filed Oct. 25, 2011, and issued U.S.Pat. No. 8,585,713, which is a continuation-in-part application of U.S.patent application Ser. No. 12/980,039, filed Dec. 28, 2010, and issuedas U.S. Pat. No. 8,066,757, which is a continuation-in part applicationof U.S. patent application Ser. No. 12/651,353, filed Dec. 31, 2009,which is a continuation-in part application of U.S. patent applicationSer. No. 12/123,390, filed May 19, 2008, which claims priority to thefollowing provisional applications: U.S. Provisional Application No.60/980,736, filed Oct. 17, 2007; U.S. Provisional Application No.60/987,384, filed Nov. 12, 2007; U.S. Provisional Application No.60/989,422, filed Nov. 20, 2007; U.S. Provisional Application No.61/015,154, filed Dec. 19, 2007; U.S. Provisional Application No.61/019,506, filed Jan. 7, 2008; and U.S. Provisional Application No.61/044,392, filed Apr. 11, 2008.

U.S. patent application Ser. No. 13/281,363 is also acontinuation-in-part application of U.S. patent application Ser. No.12/123,390, filed May 19, 2008, which claims priority to the followingprovisional applications: U.S. Provisional Application No. 60/980,736,filed Oct. 17, 2007; U.S. Provisional Application No. 60/987,384, filedNov. 12, 2007; U.S. Provisional Application No. 60/989,422, filed Nov.20, 2007; U.S. Provisional Application No. 61/015,154, filed Dec. 19,2007; U.S. Provisional Application No. 61/019,506, filed Jan. 7, 2008;and U.S. Provisional Application No. 61/044,392, filed Apr. 11, 2008.

U.S. patent application Ser. No. 13/281,363 is a continuation of U.S.patent application Ser. No. 13/172,778, filed Jun. 29, 2011, which is acontinuation-in-part application of the following applications: U.S.patent application Ser. No. 12/980,039, filed Dec. 28, 2010, and issuedas U.S. Pat. No. 8,066,757; International Application No.PCT/US2010/062532, filed Dec. 30, 2010; U.S. patent application Ser. No.12/123,390, filed May 19, 2008; U.S. patent application Ser. No.12/136,737, filed Jun. 10, 2008, and issued as U.S. Pat. No. 8,926,680;U.S. patent application Ser. No. 12/182,370, filed Jul. 30, 2008, U.S.patent application Ser. No. 12/422,105, filed Apr. 10, 2009, and issuedas U.S. Pat. No. 8,545,514; U.S. patent application Ser. No. 12/475,389,filed May 29, 2009, and issued as U.S. Pat. No. 8,088,140, which claimspriority to U.S. Provisional Application No. 61/057,613, filed May 30,2008; U.S. patent application Ser. No. 12/711,100, filed Feb. 23, 2010;and U.S. application Ser. No. 12/753,812, filed Apr. 2, 2010, whichclaims priority to U.S. Provisional Application No. 61/166,725, filedApr. 4, 2009.

This application is related to the following commonly-owned application:U.S. patent application Ser. No. 12/469,462, filed May 20, 2009.

The entire contents of each of the above-listed applications are herebyexpressly incorporated by reference herein.

FIELD

The present disclosure generally relates to devices, systems, andmethods for use in the treatment of vascular issues. More particularly,several embodiments relate to systems and methods for providing earlyblood flow restoration, maceration of an embolus, lysis of the embolus,and retrieval of any non-lysed portions of the embolus.

BACKGROUND

The pathological course of a blood vessel that is blocked is a gradualprogression from reversible ischemia to irreversible infarction (celldeath). A stroke is often referred to as a “brain attack” and occurswhen a blood vessel in the brain becomes blocked or ruptures. Anischemic stroke occurs when a blood vessel in the brain becomes blocked.Occlusions may be partial or complete, and may be attributable to one ormore of emboli, thrombi, calcified lesions, atheroma, macrophages,lipoproteins, any other accumulated vascular materials, or stenosis.Ischemic strokes account for about 78% of all strokes. Hemorrhagicstrokes, which account for the remaining 22% of strokes, occur when ablood vessel in the brain ruptures. Stroke is the third leading cause ofdeath in the United States, behind heart disease and cancer and is theleading cause of severe, long-term disability. Each year roughly 700,000Americans experience a new or recurrent stroke. Stroke is the number onecause of inpatient Medicare reimbursement for long-term adult care.Total stroke costs now exceed $45 billion per year in US healthcaredollars. An occlusion in the cerebral vasculature can destroy millionsof neurons and synapses of the brain.

SUMMARY

If not addressed quickly, the destruction of neurons and synapses of thebrain after a stroke can result in slurred speech, paralysis, loss ofmemory or brain function, loss of motor skills, and even death. Thus,there remains a need for systems, methods, and devices for the treatmentof acute ischemic stroke that provide immediate blood flow restorationto a vessel occluded by a clot and, after reestablishing blood flow,address the clot itself. Immediate blood flow restoration distal to theclot or occlusion reduces the destruction to neurons andneurovasculature. Immediate blood flow restoration facilitates naturallysis of the clot and also can reduce or obviate the concern for distalembolization due to fragmentation of the clot. There also remains a needfor systems, methods and devices for the treatment of acute ischemicstroke that provide for progressive treatment based upon the nature ofthe clot, wherein the treatment involves immediate restoration of bloodflow, in-situ clot management, and clot removal depending on theparticular circumstances of the treatment. The progressive treatment canbe provided by a kit of one or more devices. According to severalembodiments of the present disclosure, clot therapy may have one or moreof at least three objectives or effects: maceration of a clot, removalof a clot, and lysis of a clot.

In accordance with several embodiments, a thrombus management method forthe treatment of ischemic stroke without distal embolic protection isprovided. In some embodiments, the thrombus management method comprisesidentifying a blood vessel (e.g., an artery of the neurovasculature)having a thrombus. In some embodiments, the method comprises inserting aguide catheter (e.g., a balloon guide catheter) into a patient. In someembodiments, the method comprises advancing a distal end of the balloonguide catheter to an arterial location proximal to the thrombus. In someembodiments, the method comprises inserting a guide wire through theguide catheter into the occluded vessel and through the thrombus. Insome embodiments, the guidewire is inserted first and then the guidecatheter is inserted over the guidewire. In several embodiments, theguidewire follows a path of least resistance through the thrombus. Insome embodiments, the guidewire does not travel through the thrombus buttravels to the side of the thrombus (for example, if the thrombus is notpositioned across the entire diameter, or height, of the vessel). Insome embodiments, the method comprises inserting a distal accesscatheter through the guide catheter and advancing a distal end of thedistal access catheter to an origin of the occluded artery. In someembodiments, the occluded artery is a middle cerebral artery and thedistal end of the distal access catheter is inserted to a locationwithin the middle cerebral artery or within an internal carotid artery.In some embodiments, the occluded artery is the basilar artery and thedistal end of the distal access catheter is inserted to a locationwithin a vertebral artery or to an origin of the basilar artery. In someembodiments, the thrombus management method comprises inserting amicrocatheter over the guidewire (which may be through the thrombus orto the side of the thrombus as described above). In some embodiments,the method comprises positioning a distal end of the microcatheterwithin about a centimeter (e.g., 0.5 to 10 mm) past the thrombus. Insome embodiments, the method further comprises positioning a distal endof the expandable tip assembly to substantially align with the distalend of microcatheter.

In some embodiments, the method comprises inserting an expandable tipassembly comprising a scaffold through the microcatheter. In someembodiments, the scaffold comprises a self-expandable scaffoldcomprising a generally cylindrical body comprised of a plurality ofstruts and bridges forming a plurality of cells, wherein the cells aresized and shaped to impact, compress and engage thrombus material uponradial expansion of the self-expandable scaffold. In some embodiments,the expandable tip assembly comprising a self-expandable scaffoldtethered to a distal end of an elongate delivery member.

In some embodiments, the method comprises retracting the microcatheterproximally, thereby causing the scaffold to expand at the location ofthe thrombus. The expansion of the scaffold can impact and compress thethrombus against a wall of the blood vessel. The compression of thethrombus can restore blood flow within the blood vessel and the restoredblood flow can facilitate natural lysis and/or fragmentation of thethrombus. In some embodiments, the thrombus management method comprisesmacerating the thrombus by resheathing the scaffold and unsheathing thescaffold (e.g., by advancing and retracting the microcatheter), therebyfacilitating mechanical lysis and fragmentation of the thrombus torelease embolic particles. The embolic particles can flow in thedirection of the blood flow and may not be captured by any distalembolic protection member, but can instead be lysed through the naturallysis process due to the restored blood flow. In some embodiments,resheathing and unsheathing the scaffold comprises movement of themicrocatheter with respect to the expandable tip assembly while theexpandable tip assembly remains stationary. Macerating the thrombus cancomprise resheathing the scaffold and unsheathing the scaffold one timeor multiple times (e.g., two times, three times, four times, five times,six times) In some embodiments, blood flow is restored in less than twominutes (e.g., about 90 seconds, 60 seconds, 30 seconds, 15 seconds,etc.) from deployment of the scaffold within the thrombus.

In some embodiments, the thrombus management method comprises capturingone or more non-lysed portions of the thrombus on the exterior surfaceof the scaffold (e.g., open cell structure of the self-expandablescaffold sized and shaped to engage, grab, or otherwise capture thrombusmaterial). In some embodiments, the thrombus management method comprisesremoving the expandable tip assembly from the subject, thereby removingthe captured non-lysed portions of the thrombus engaged by the scaffoldfrom the occluded artery. In some embodiments, the one or more non-lysedportions comprises an inner core of the thrombus.

In some embodiments, the thrombus management method comprises providinglocal aspiration at a location proximal to the thrombus within theoccluded artery through the distal access catheter. In some embodiments,the method comprises providing proximal aspiration at a locationproximal to and remote from the location of thrombus through the balloonguide catheter.

In some embodiments, the thrombus management method comprises engaging aremaining portion of the thrombus after said maceration and extractingor removing said remaining portion of the thrombus from the bloodvessel. The engaging and extracting of the remaining portion of thethrombus can be performed by the expandable tip assembly that performedthe blood flow restoration and/or maceration (e.g., the first expandabletip assembly) or by a second expandable tip assembly configured oradapted for thrombus removal. If a second expandable tip assembly isused, the second expandable tip assembly can be inserted into themicrocatheter after removing the first expandable tip assembly from themicrocatheter after macerating the thrombus. The first expandable tipassembly can comprise a self-expanding scaffold with open cells having acell size configured or adapted to facilitate blood flow restoration andnatural lysis of the thrombus. The second expandable tip assembly cancomprise a self-expanding scaffold with open cells having a cell sizeconfigured to increase penetration, or protrusion, of the remainingthrombus material into the cells to facilitate capture of the remainingthrombus material.

In some embodiments, the thrombus management method comprises deliveringone or more agents configured to promote thrombus adhesion or plateletactivation or one or more lytic agents to a location of the thrombusthrough or over the expandable tip assembly. For example, the agents canbe infused through a lumen of the expandable tip assembly or around theexpandable tip assembly through a lumen of the microcatheter.

In accordance with several embodiments of the invention, a thrombusmanagement method comprises identifying a blood vessel having anocclusive thrombus and selecting an expandable tip assembly based, atleast in part, on a diameter of the identified occluded blood vessel.The expandable tip assembly can comprise a proximal elongate member anda distal self-expanding scaffold. In some embodiments, the methodcomprises inserting the selected expandable tip assembly within theoccluded vessel through a microcatheter such that the self-expandingscaffold is positioned at a location of (e.g., to coincide with theposition of) the thrombus in a non-expanded configuration. Positioningthe self-expanding scaffold at a location of the thrombus can refer to alocation that spans (partially or completely) the thrombus. For example,if a thrombus in a vessel has a height and a length, wherein the lengthis substantially parallel with the longitudinal axis of the vessel,spanning the thrombus includes, but is not limited to, positioning adevice to extend partially across the length of the thrombus, to extendfrom one end of the thrombus to the other end of the thrombus, or toextend past (e.g., just past, such as 0.5 to 5 mm past, 1 mm to 10 mmpast, or overlapping ranges thereof)) one or both ends of the thrombus.Depending on whether the height of the thrombus extends along the entireheight, or diameter, of the vessel, the non-expanded device may be incontact with a portion of the thrombus or may not be in contact with thethrombus. The self-expanding scaffold can be positioned either withinthe thrombus or outside the thrombus (e.g., depending on the location ofthe microcatheter and the size of the thrombus). The microcatheter canthen be retracted, thereby causing the scaffold to expand to an expandedconfiguration. The expansion can compress the thrombus against a wall ofthe blood vessel, thereby restoring blood flow within the blood vesselby creating a bypass channel through or past the thrombus. The restoredblood flow facilitates natural lysis of the thrombus. In someembodiments, the proximal elongate member of the expandable tip assemblycomprises a flexible, distal portion configured to navigate curvedportions of the cerebral vasculature.

In accordance with several embodiments of the invention, a method forproviding multiple layer embolus removal from a cerebral artery isprovided. In some embodiments, the method comprises identifying anembolus within a cerebral artery and inserting an expandable reperfusiondevice within the cerebral artery to the location of the embolus (e.g.,positioned to coincide with a position of the embolus). The embolus, orthrombus, can comprise one or more soft outer layers and a firm fibrincore. In some embodiments, the method comprises expanding thereperfusion device within the embolus, thereby establishing one or moreblood flow channels through or past the embolus. The one or more bloodflow channels facilitate natural lysis of the embolus to remove one ormore outer layers of the embolus. The one or more outer layers of theembolus can comprise platelets and red blood cells.

In some embodiments, the method comprises removing the reperfusiondevice and inserting an expandable embolus removal device within thecerebral artery to the location of the embolus. In some embodiments, themethod comprises expanding the embolus removal device within a remainingportion of the embolus, thereby engaging the remaining portion of theembolus. In some embodiments, the method comprises extracting theremaining portion of the embolus with the embolus removal device fromthe cerebral artery by removing the embolus removal device.

In some embodiments, the reperfusion device comprises an expandable tipassembly including a proximal elongate member and a distalself-expanding scaffold. The scaffold of the reperfusion device cancomprise open cells having a cell size that is configured to decrease,hinder, prevent, deter, discourage, inhibit, or reduce penetration, orprotrusion, of the embolus within the scaffold, thereby increasing bloodflow through the scaffold because the flow channel through the scaffoldis larger. In some embodiments, the embolus removal device comprises anexpandable tip assembly including a proximal elongate member and adistal self-expanding scaffold. The scaffold of the embolus removaldevice can comprise open cells having a cell size that is configured toincrease, promote, facilitate, enhance, allow, or enable penetration, orprotrusion, of the remaining portion of the embolus material within thescaffold to facilitate capture of the remaining portion of the embolus.The cell size of the embolus removal device can be larger than the cellsize of the reperfusion device.

In accordance with some embodiments, a method for providing multiplelayer embolus removal comprises identifying an embolus having an outerlayer and an inner core. In some embodiments, the method comprisesestablishing one or more blood flow channels through the embolus torestore blood flow. In one embodiment, establishing one or more bloodflow channels comprises inserting an expandable reperfusion scaffoldwithin or adjacent the thrombus and expanding it. In some embodiments,the method comprises disturbing the embolus by mechanical maceration ofthe embolus to release embolic particles from the outer layer, therebyallowing the embolic particles to freely flow in the direction of theblood flow without capturing said embolic particles. Free flow can referto downstream flow without obstruction or capture, such as a distalembolic protection device (e.g., a basket, a net, a filter). Thedisturbance may be caused by maceration of the embolus with anexpandable scaffold, thereby enhancing lysis of the embolic particles.In some embodiments, restored blood flow causes further release ofembolic particles from the outer layer of the embolus. In someembodiments, the method comprises extracting the inner core of theembolus. The one or more outer layers of the embolus can comprise softerlayers than the inner core of the embolus. The inner core can comprise afibrin core that has a hardness that exceeds the one or more outerlayers of the embolus.

In accordance with several embodiments of the invention, a method forproviding progressive therapy for thrombus management in blood vesselsis provided. In some embodiments, the method comprises identifying athrombus within a blood vessel. In some embodiments, the methodcomprises inserting an expandable reperfusion device within the bloodvessel to the location of the thrombus. The expandable reperfusiondevice can comprise an expandable reperfusion scaffold having aplurality of interconnected struts that form cells having a cell sizethat is sized and configured to reduce, prevent, hinder, or deterpenetration, or protrusion, of the thrombus into the reperfusionscaffold, thereby increasing a diameter of a flow path established bythe reperfusion scaffold. In some embodiments, the method comprisesdeploying the reperfusion device within the thrombus, therebycompressing the thrombus against the inner vessel wall and establishingone or more blood flow channels through the thrombus. The one or moreblood flow channels can facilitate natural lysis of the thrombus. Insome embodiments, the method comprises removing the reperfusion device.

In some embodiments, the method for providing progressive therapy forthrombus management of blood vessels comprises inserting an expandablethrombus removal device within the blood vessel to the location of thethrombus. The expandable thrombus removal device can comprise anexpandable removal scaffold having a plurality of interconnected strutsthat form cells having a cell size that is sized and configured to allowthrombus penetration, or protrusion, within the cells, therebyfacilitating engagement of the thrombus by the removal scaffold. In someembodiments, the method comprises deploying the thrombus removal devicewithin a remaining portion of the thrombus, thereby engaging theremaining portion of the thrombus. In some embodiments, the methodcomprises extracting the remaining portion of the thrombus engaged bythe thrombus removal device from the blood vessel. In some embodiments,the method comprises removing the thrombus removal device.

In some embodiments, the expandable reperfusion device and/or theexpandable thrombus removal device comprise self-expanding devices. Insome embodiments, the expandable reperfusion device and the expandablethrombus removal device are inserted into the blood vessel within amicrocatheter. In some embodiments, deploying the reperfusion devicecomprises retracting the microcatheter, thereby allowing the reperfusiondevice to expand within the thrombus. In some embodiments, deploying thethrombus removal device comprises retracting the microcatheter, therebyallowing the thrombus removal device to expand within the thrombus. Insome embodiments, removing the reperfusion device comprises resheathingthe reperfusion device by advancing the microcatheter over thereperfusion device while keeping the reperfusion device stationary andthen removing the microcatheter with the reperfusion device together. Insome embodiments, the method comprises resheathing the reperfusiondevice within the microcatheter by advancing the microcatheter and thenunsheathing the reperfusion device by retracting the microcatheter toprovide maceration of the thrombus.

In some embodiments, an expansion diameter of the reperfusion device isconfigured to provide increased cell deformation of the reperfusionscaffold, thereby reducing thrombus penetration or protrusion, withinthe reperfusion scaffold. In some embodiments, an expansion diameter ofthe thrombus removal device is configured to provide reduced celldeformation of the removal scaffold, thereby increasing thrombuspenetration, or protrusion, within the removal scaffold. In someembodiments, the cells of the reperfusion scaffold in an expandedconfiguration have a cell length of between 2 mm and 4 mm and a cellheight between 1 mm and 3 mm and wherein the cells of the removalscaffold in an expanded configuration have a have a cell length ofbetween 4 mm and 6 mm and a cell height between 2 mm and 4 mm.

In accordance with several embodiments of the invention, a method forproviding progressive therapy for thrombus management is provided. Insome embodiments, the method comprises inserting an expandablereperfusion device within an occluded blood vessel having a thrombus. Insome embodiments, the method comprises positioning the expandablereperfusion device to span at least a portion of a length of thethrombus. The expandable reperfusion device can comprise aself-expanding reperfusion scaffold having a plurality of interconnectedstruts that form cells sized and configured to inhibit penetration, orprotrusion, of the thrombus into the reperfusion scaffold, therebyincreasing a diameter of a flow path established by the reperfusionscaffold. In some embodiments, the method comprises deploying thereperfusion device within the thrombus, thereby compressing the thrombusagainst the inner vessel wall and establishing blood flow through theoccluded blood vessel. The established blood flow facilitates naturallysis of the thrombus. In some embodiments, the method comprisesmacerating the thrombus (for example, by resheathing and unsheathing thereperfusion scaffold). At least one of the natural lysis and themaceration can fragment the thrombus until only a portion of thethrombus remains. In some embodiments, the method comprises removing thereperfusion device.

In some embodiments, the method for providing progressive therapy forthrombus management comprises inserting a thrombus removal device withinthe blood vessel to span at least a portion of a length of the remainingthrombus. The thrombus removal device can comprise a self-expandingremoval scaffold having a plurality of interconnected struts that formcells having a cell size that is sized and configured to allow orfacilitate thrombus penetration, or protrusion, within the cells,thereby facilitating engagement of the remaining thrombus by the removalscaffold. In some embodiments, the method comprises deploying thethrombus removal device within the remaining thrombus to engage theremaining thrombus. In some embodiments, the method comprises removingthe thrombus removal device, thereby extracting the remaining thrombus.

In accordance with several embodiments of the invention, a system forproviding progressive therapy for clot management is provided. In someembodiments, the system comprises a microcatheter. In some embodiments,the clot management system comprises a first expandable tip assemblycomprising a first elongate member and a first self-expanding scaffold.In some embodiments, the first self-expanding scaffold comprises opencells formed by a pattern of struts and bridges. The cells can have acell size configured to hinder, inhibit, or reduce penetration, orprotrusion, of clot material within the scaffold, thereby increasing anamount of blood flow through the scaffold. In some embodiments, thesystem comprises a second expandable tip assembly comprising a secondelongate member and a second self-expanding scaffold. In someembodiments, the second self-expanding scaffold comprises open cellsformed by a pattern of struts and bridges. The cells of theself-expanding scaffold can have a cell size larger than the cell sizeof the first self-expanding scaffold. The larger cell size can beconfigured to enhance penetration, or protrusion, of clot materialwithin scaffold to facilitate capture of the thrombus.

In some embodiments, the first elongate member and the second elongatemember comprise a variable-stiffness hypotube having a lumen. Thevariable stiffness can be created by intermittently-spaced spiral lasercuts. The cuts can be spaced so as to provide increased flexibilitytoward the distal end of the hypotube. In some embodiments, the cuts arespaced closer together toward the distal end of the hypotube. In someembodiments, the laser spiral cut pattern allows the distal section tobend to navigate through tortuous, curved portions of the cerebralvasculature (e.g., the carotid siphon). In some embodiments, the laserspiral cut pattern spans a length of at least about 35 cm from thedistal end of the hypotube. In some embodiments, the system comprises aguidewire configured to be received by the first elongate member and thesecond elongate member. The first and second expandable tip assembliescan be delivered over the guidewire. The guidewire can providemaintained access to the treatment site during removal of the firstexpandable tip assembly and insertion of the second expandable tipassembly.

In some embodiments, the first elongate member and/or the secondelongate member comprise a wire without a lumen. In some embodiments,the first self-expanding scaffold and the second self-expanding scaffoldhave an average chronic outward force across a diameter of 1.5 mm to 4.5mm that does not decrease by more than 10% to 90%, by more than 50% to75%, by more than 25% to 60%, by more than 40% to 85%, or overlappingranges thereof. In some embodiments, the average chronic outward forceis non-zero across an expansion diameter of 1 mm to 4.5 mm.

In accordance with several embodiments of the invention, a thrombusmanagement system for providing progressive therapy is provided. In someembodiments, the system comprises a microcatheter configured to beinserted within a blood vessel (e.g., cerebral artery) having anocclusive thrombus. In some embodiments, the system comprises atemporary expandable reperfusion device configured to be insertedthrough the microcatheter to treat the thrombus. The expandablereperfusion device can comprise a self-expanding scaffold having aplurality of interconnected struts that form cells having a cell sizethat is sized and configured to hinder penetration of the thrombus intothe self-expanding scaffold, thereby increasing a diameter of a flowpath established by the expandable scaffold. In some embodiments, thesystem comprises a temporary expandable thrombus removal deviceconfigured to be inserted through the microcatheter to treat thethrombus. The expandable thrombus removal device can comprise aself-expanding scaffold having a plurality of interconnected struts thatform cells having a cell size that is sized and configured to facilitatethrombus penetration within the cells, thereby increasing engagement ofthe thrombus by the self-expanding scaffold.

In some embodiments, the cells of the scaffold of the expandablereperfusion device have a cell length of between 2 mm and 4 mm (e.g., 2,2.5, 3, 3.5, 4 mm) and a cell height between 1 mm and 3 mm (e.g., 1,1.5, 2, 2.5, 3 mm) in an expanded configuration. In some embodiments,the ratio of the length and the height is about 4:1, 3:1, 2:1, 1:1, 1:2,1:3 or 1:4. The cells may have the same dimensions or differentdimensions in a single scaffold. Layers of cells or multiple scaffoldscan be used to, for example, provide different cell sizes. In someembodiments, the scaffold of the expandable reperfusion device has achronic outward force across an expansion diameter of 1.5 mm to 4.5 mm(e.g., 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, 4.0 mm of between 0.0040N and 0.0120 N (e.g., between 0.0040 N and 0.0100 N, between 0.0060 Nand 0.0120 N, about 0.0040N, about 0.0050 N, about 0.0060 N, about0.0070 N, about 0.0080 N, about 0.0090 N, about 0.0100 N, about 0.0110N, about 0.0120 N). In some embodiments, the chronic outward force is anaverage chronic outward force. In some embodiments, the cells of thescaffold of the expandable thrombus removal device in an expandedconfiguration have a cell length of between 4 mm and 6 mm and a cellheight between 2 mm and 4 mm. In some embodiments, the expandablethrombus removal device has an average chronic outward force across adiameter of 1.5 mm to 4.5 mm of between 0.0020 N and 0.0090 N. In someembodiments, a central portion of each strut of the expandable thrombusremoval device has a greater thickness than adjacent portions of thestrut. In several embodiments, the central portion of the strutcomprises the middle 10%, 20%, 25%, 30%, 35%, 40% or 50% of the strut.In some embodiments, the central portion of the strut is about 5%, 10%,15%, or 20% thicker than the adjacent portions and/or the end portions.In one embodiment, the central portion is thicker than the adjacentportions, which in turn are thicker (or thinner) than the end portions.In another embodiment, the central portion is thicker than the adjacentportions, wherein the adjacent portions have the same thickness as theend portions.

In accordance with several embodiments of the invention, a system forproviding progressive therapy for clot management is provided. In someembodiments, the clot management system comprises a microcatheter (e.g.,a neuro microcatheter). In some embodiments, the system comprises avariable-stiffness, laser-cut hypotube having a lumen sized and adaptedto receive a guidewire. The distal end of the hypotube can have agreater flexibility than the proximal end to facilitate introductionwithin tortuous cerebral vasculature (e.g., the carotid siphon).

In some embodiments, the system comprises an expandable andreconstrainable scaffold coupled to a distal end of the hypotube. Thescaffold can be adapted to radially self-expand from a non-expandedconfiguration to an expanded configuration upon unsheathing of thescaffold and adapted to transition from the expanded configuration tothe non-expanded configuration upon sheathing of the scaffold. In someembodiments, the scaffold comprises a generally cylindricalconfiguration. In some embodiments, the scaffold comprises an undulatingconfiguration, a tapered or conical configuration, a triangularconfiguration, an elliptical configuration, a spiral configuration, orother configuration. In some embodiments, the scaffold comprises aplurality of open cells defined by struts and connected by bridges. Insome embodiments, each strut of the scaffold has a strut width and astrut thickness providing effective pinching stiffness and hoopstiffness for compressing a vascular clot to promote at least one oflysis, maceration, and removal of the clot without compromisingtrackability of the stroke device. In some embodiments, the struts havea squared-off configuration, a rounded configuration, a pointedconfiguration (e.g., tapered, wedge-shaped, triangular), and/or agrooved configuration. In some embodiments, struts having a pointedconfiguration are adapted to facilitate penetration into a thrombus orclot, thereby facilitating protrusion of thrombus material within aninterior of the scaffold through the cells of the scaffold, and therebyfacilitating engagement of the thrombus material by the scaffold. Theenhanced engagement of the thrombus material increases the likelihood ofcomplete removal of the thrombus material in a single pass. In someembodiments, the exterior contact surfaces of the struts are textured orinclude surface features designed to facilitate engagement or adhesionof thrombus material (e.g., ridges, bumps, grooves, cut-outs, recesses,serrations, etc.). In some embodiments, the struts are coated with oneor more materials adapted to promote platelet activation or adhesion ofthrombus material.

In some embodiments, the system for providing progressive therapy forclot management comprises a guidewire configured to be received by thelumen of the hypotube. In some embodiments, the scaffold has a chronicoutward force (COF) per unit length that does not decrease by more than75% from a diameter of 1.5 mm to a diameter of 4.5 mm. In someembodiments, the scaffold has a chronic outward force (COF) per unitlength that does not decrease by more than 95%, 90%, 85%, 80%, 75%, 70%,65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, or 10%. In someembodiments, each bridge of the scaffold is connected by three or fourstruts. In some embodiments, the scaffold comprises a closed-cellscaffold to facilitate resheathing. In some embodiments, a distal end ofthe elongate member is soldered to a proximal end of the scaffold usinga radiopaque band comprising a different material than the elongatemember and the scaffold.

In accordance with several embodiments of the invention, an expandabletip assembly is provided. In some embodiments, the expandable tipassembly comprises an elongate member. The elongate member can include ahypotube having a lumen or a wire (e.g., guidewire or delivery wire)without a lumen. In some embodiments, the hypotube can comprise avariable-stiffness hypotube having a proximal portion, a distal portionand a lumen sized and adapted to receive a guidewire. In someembodiments, the distal portion of the hypotube has a greaterflexibility than the proximal portion to facilitate introduction withintortuous cerebral vasculature. In some embodiments, the greaterflexibility is provided by spiral laser cuts spaced along the distalportion of the hypotube. The spacing between the spiral cuts candecrease from a proximal end of the distal portion to a distal end ofthe distal portion. In some embodiments, the expandable tip assemblycomprises a self-expanding scaffold coupled to a distal end of theelongate member. The self-expanding scaffold can be detachably coupledor permanently coupled (e.g., non-detachably, non-releasably) to thedistal end of the elongate member. In some embodiments, the scaffold iscoupled to the distal end of the elongate member by a plurality oftether lines. The tether lines can extend concentrically oreccentrically from (e.g., from one side, from one half, from belowcenter, from above center) of the distal end of the elongate member. Insome embodiments, the scaffold is adapted to radially expand from anon-expanded configuration to an expanded configuration upon unsheathingof the scaffold and is adapted to transition from the expandedconfiguration to the non-expanded configuration upon unsheathing andresheathing of the scaffold. In some embodiments, the scaffold comprisesa generally cylindrical configuration. In some embodiments, the scaffoldcomprises an open distal end without a distal embolic protection memberor device. In some embodiments, a proximal end of the scaffold comprisesa cut-out portion configured to facilitate re-sheathing of the scaffold.In some embodiments, the scaffold comprises a plurality of open cellsdefined by struts and connected by bridges. In some embodiments, eachstrut has two ends, with each end connected to one of the bridges. Insome embodiments, each bridge is connected to four struts. In someembodiments, the struts and the bridges have varying thickness to impartflexibility to the scaffold. For example, a central portion of eachstrut can have a greater thickness than adjacent portions of the strut.As another example, a central portion of each strut can have a greaterwidth than adjacent portions of the strut.

In some embodiments, the scaffold has a chronic outward force per unitlength that does not decrease by more than 75% from a diameter of 1.5 mmto a diameter of 4.5 mm. In some embodiments, the scaffold has a chronicoutward force per unit length that does not decrease by more than 50%from a diameter of 1.5 mm to a diameter of 4.5 mm. In some embodiments,the open cells have a cell size of about 5 mm by about 3 mm. In someembodiments, the scaffold comprises nitinol, stainless steel, nickeltitanium alloy, and/or other shape memory materials.

In accordance with several embodiments of the invention, an expandabletip assembly comprises a self-expanding scaffold having an average COFper unit length across a diameter of 2.0 mm to 4.5 mm of between atleast about 0.0025 N/mm and at least about 0.007 N/mm, between at leastabout 0.0030 N/mm and at least about 0.0059 N/mm, between at least about0.00165 N/mm and at least about 0.0090 N/mm, or overlapping rangesthereof. In some embodiments, the scaffold has a radial resistive force(RRF) range per unit length across a diameter of 2.0 mm to 4.5 mm ofbetween at least about 0.005 N/mm and at least about 0.016 N/mm. In someembodiments, the ratio of strut thickness to strut width is less than atleast about 1:4 (e.g., 1:4, 1:4.5, 1:5, 1.5:.5, 1:6). In someembodiments, the strut thickness is substantially equal to the strutwidth or greater than the strut width. The struts can be substantiallylinear across their length or at least a portion of the struts can havea curve. In some embodiments, the open cells of the scaffold aresubstantially diamond-shaped or parallelogram-shaped, and the bridgesare substantially “C”-shaped, substantially “U”-shaped, substantially“S”-shaped, or substantially “X”-shaped. In some embodiments, each opencell is defined by six struts. In some embodiments, the cells of thescaffold have an area that varies between about 0.010 sq. inches andabout 0.020 sq. inches. In some embodiments, each of the cells has thesame area. In some embodiments the open cells have a length from about0.120 inches to about 0.250 inches and a height from about 0.050 inchesto about 0.100 inches when the scaffold is in an expanded configuration.In some embodiments, the ratio between the length of the cells and theheight of the cells is 1:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1,3:2, 4:3, 5:3, 1:2, 1:3, or 1:4. In some embodiments the scaffold has alength of about 30 mm. In some embodiments, the scaffold has a lengthfrom about 5 mm to about 50 mm, from about 10 mm to about 40 mm, fromabout 15 mm to about 35 mm, from about 20 mm to about 40 mm, oroverlapping ranges thereof.

In accordance with several embodiments of the invention, a kit isprovided for providing progressive therapy to address an occlusivethrombus. In some embodiments, the kit comprises a plurality ofexpandable tip assemblies, such as those described herein. For example,the kit can comprise a first expandable tip assembly, or reperfusiondevice, that is adapted to facilitate reperfusion of a blood vesseloccluded by a thrombus, and therefore, facilitate lysis of the thrombus.The first expandable tip assembly, or reperfusion device, can comprise aproximal elongate member and a self-expanding scaffold coupled to adistal end of the proximal elongate member. The elongate member cancomprise a wire without a lumen or a tube with a lumen. Theself-expanding scaffold can comprise cells having a cell size adapted tohinder, inhibit, or reduce the likelihood of penetration within aninterior of the scaffold upon expansion of the scaffold adjacent to,across, or within, the thrombus. In some embodiments, the kit comprisesa second expandable tip assembly, or thrombus removal device, that isadapted to facilitate engagement with, capture, and/or extraction ofthrombus material. In some embodiments, the second expandable tipassembly can be used after the first expandable tip assembly to removeany thrombus material remaining after use of the first expandable tipassembly. In some embodiments, the second expandable tip assembly, orthrombus removal device, comprises a proximal elongate member and aself-expanding scaffold coupled to a distal end of the proximal elongatemember. The elongate member can comprise a wire without a lumen or atube with a lumen. The self-expanding scaffold of the second expandabletip assembly can comprise cells having a cell size adapted tofacilitate, promote, or increase the likelihood of penetration within aninterior of the scaffold upon expansion of the scaffold adjacent to,across, or within, the thrombus, thereby facilitating engagement with,and capture of, the thrombus.

In some embodiments, the kit comprises a microcatheter, such as aneuro-microcatheter. The microcatheter can be adapted to deliver theexpandable tip assemblies within blood vessels. The microcatheter can besized so as to be inserted within cerebral vasculature of a humanpatient (e.g., an outer diameter of less than 0.040 inches, less than0.030 inches, less than 0.025 inches). In some embodiments, themicrocatheter provides a sheathing function as described in more detailherein. In some embodiments, the kit comprises a guidewire. In someembodiments, the microcatheter and the expandable tip assemblies can bedelivered over the guidewire, thereby providing maintained access to theocclusive thrombus during removal of a first expandable tip assembly andinsertion of a second expandable tip assembly or during repositioning ofan expandable tip assembly. In some embodiments, the kit comprises aguide catheter adapted to access vasculature of a patient (e.g., afemoral artery) and adapted to be inserted within the vasculature to aregion near the cerebral vasculature. The guide catheter can be sized toreceive the microcatheter. The kit can be provided with instructions foruse.

In some embodiments, a kit is provided that includes a plurality ofexpandable tip assemblies having varying maximum expansion diameters tobe inserted within vessels having varying diameters. The kit ofdifferently-sized expandable tip assemblies can provide adjustabletargeted treatment options depending on a location of a clot. Theexpandable tip assemblies can be selected based on the location of theclot. An appropriately-sized expandable tip assembly can be selected toreduce or increase cell deformation and/or wall apposition. For example,an expandable tip assembly having a maximum expansion diameter of 3 mmcan be adapted for use in the M1 or M2 segment of the middle cerebralartery and an expandable tip assembly having a maximum expansiondiameter of 5 mm can be adapted for use in the internal carotid artery.The kit can be provided with instructions for use.

In some embodiments, the expandable scaffolds or self-expandingscaffolds described herein include cells having variable cell size atdifferent portions of the scaffold. For example, the scaffolds can haverelatively smaller cells at one or both distal end portions of thescaffold and relatively larger cells at a middle portion of thescaffold. Portions of the scaffold having relatively small cell sizes(e.g., reperfusion portions) can be configured to provide or facilitateeffective blood flow restoration or reperfusion and the portions of thescaffold having relatively large cell sizes (e.g., removal portions) canbe configured to provide or facilitate effective clot removal. In someembodiments, the cell size can be configured to provide or facilitateeffective blood flow restoration or reperfusion and effective clotremoval.

For purposes of summarizing the disclosure, certain aspects, advantagesand novel features of various embodiments have been described herein. Itis to be understood that not necessarily all such advantages may beachieved in accordance with any particular embodiment disclosed herein.Thus, embodiments disclosed herein may be embodied or carried out in amanner that achieves or selects one advantage or group of advantages astaught herein without necessarily achieving other advantages as may betaught or suggested herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The features of embodiments of the inventions disclosed herein aredescribed below with reference to the drawings. Throughout the drawings,reference numbers are re-used to indicate correspondence betweenreferenced elements. The drawings are provided to illustrate embodimentsof the inventions described herein and not to limit the scope thereof.

FIG. 1 is an illustration of the anatomy of the human cerebralvasculature or neurovasculature.

FIGS. 2A and 2B illustrate an embodiment of an acute strokerecanalization system tailored for use in the neurovasculature of FIG.1, further illustrating modular aspects of the system as used withtethered or reconstrainable self-expanding neurological medical devices.

FIG. 2C illustrates a close-up view of the inner catheter of FIG. 2B.

FIGS. 3 and 3A illustrate schematic representations of embodiments of arevascularization system being used to address a clot in an occludedvessel.

FIGS. 4 and 5 illustrate expandable scaffolds having variable cell sizesand patterns.

FIGS. 6A-6C illustrate an embodiment of an expandable tip assembly.

FIG. 6D illustrates another embodiment of an expandable tip assembly.

FIGS. 7A and 7B illustrate a side view and a front view of an embodimentof an elongate member of an expandable tip assembly.

FIGS. 7C and 7D illustrate embodiments of delivery device assemblies.

FIGS. 8A-8C illustrate a perspective view, a side view, and a frontview, respectively, of an embodiment of an expandable scaffold.

FIGS. 9A-9C illustrate a side view, a top view, and a front view of anembodiment of an expandable scaffold.

FIGS. 10A-10C illustrate a perspective view, a side view and a frontview of one embodiment of an expandable scaffold in a compressedconfiguration and FIGS. 10D-10F illustrate a perspective view, a sideview and a front view of the expandable scaffold in an expandedconfiguration.

FIG. 11A illustrates a side view of an embodiment of an expandablescaffold in a compressed configuration and FIGS. 11B and 11C illustratea perspective view and a side view of the expandable scaffold of FIG.11A in an expanded configuration.

FIG. 12A illustrates a laser cut profile of an embodiment of anexpandable scaffold. FIGS. 12B and 12C illustrate a perspective view anda side view of the expandable scaffold formed from the cut profile ofFIG. 12A in its expanded configuration. FIG. 12D illustrates atwo-dimensional view of the cut profile of FIG. 12A in its expandedconfiguration.

FIGS. 13A and 13B illustrate two-dimensional cut profiles of anembodiment of an expandable scaffold in its compressed and expandedconfigurations, respectively.

FIG. 14 illustrates a laser cut profile of the expandable scaffold ofFIGS. 8A-8C.

FIG. 15A illustrates a laser cut profile of an embodiment of anexpandable scaffold and FIGS. 15B and 15C illustrate a perspective viewand a side view of the expandable scaffold formed from the laser cutprofile of FIG. 15A in its expanded configuration.

FIG. 16 illustrates a laser cut profile of the expandable scaffold ofFIGS. 9A-9C.

FIG. 17A illustrates a laser cut profile of an embodiment of an offsetexpandable scaffold and FIGS. 17B-17E illustrate a side view, a frontview, a back view, and a section view of the expandable scaffold formedfrom the laser cut profile of FIG. 17A.

FIGS. 18A-18C illustrate a perspective view, a side view, and a frontview of an embodiment of a spiral expandable scaffold in its compressedconfiguration and FIGS. 18D-18F illustrate a perspective view, a sideview, and a front view of the spiral expandable scaffold in its expandedconfiguration.

FIG. 19 illustrates a perspective view of an embodiment of an expandablescaffold.

FIG. 20 illustrates a perspective view of an embodiment of a wovenexpandable scaffold configured for clot retrieval.

FIG. 21A shows an embodiment of an expandable scaffold in cross sectionhaving an unexpanded state and an expanded state.

FIG. 21B shows an embodiment of an expandable scaffold in cross sectionhaving a first state and a second state under pinching load.

FIG. 22 shows a cell of one embodiment of an expandable scaffold with aportion in an expanded view.

FIG. 23 shows a cell of one embodiment of an expandable scaffold with acell thereof in an expanded view.

FIGS. 24A, 24B, 25A 25B, 26A, 26B, 27A, and 27B show a variety of cellsizes and geometries that may be provided to achieve desired outcomesduring therapy.

FIGS. 28, 29A, 29B and 29C show a variety of individual cell sizes, withemphasis.

FIG. 30A shows a perspective view of an expandable scaffold and aclose-up detailed view of a cell of one embodiment of an expandablescaffold.

FIG. 30B shows a detailed schematic representation of a cell of oneembodiment of an expandable scaffold.

FIGS. 31A-31D illustrate various embodiments of strut profiles.

FIGS. 32A-32F illustrate various embodiments of expandable scaffoldprofiles or shape configurations.

FIGS. 33A-33F illustrate an embodiment of a revascularization process.

FIGS. 34A and 34B illustrate eccentric or offset deployment of aguidewire through an embolus, in accordance with an embodiment of theinvention.

FIG. 35 illustrates a schematic representation of a portion of thecerebral vasculature.

FIG. 36 illustrates an embolus positioned adjacent a junction of aportion of the cerebral vasculature.

FIG. 37 is a flow diagram of an embodiment of a stroke treatment processfor performing progressive, or modular, stroke therapy.

FIG. 38 illustrates deployment of an embodiment of an expandable tipassembly being delivered as a component of a rapid exchangecatheter-based revascularization system.

FIG. 39 is an illustration of a balloon catheter and delivery system,with a balloon in a deflated state, according to several embodiments ofthe present disclosure.

FIG. 40 is an illustration of a balloon catheter and delivery system,with a balloon in an inflated state, according to several embodiments ofthe present disclosure.

FIG. 41 is an illustration of a balloon catheter and delivery system,with a cage-like structure in a deployed state, according to severalembodiments of the present disclosure.

FIG. 42 is cross-sectional view of a balloon catheter and deliverysystem, with a cage-like structure in a retracted state, according toseveral embodiments of the present disclosure.

FIG. 43 is an illustration of a balloon catheter and delivery systemshown approaching an occlusion, according to several embodiments of thepresent disclosure.

FIG. 44 is an illustration of a balloon catheter and delivery systemshown crossing an occlusion, according to several embodiments of thepresent disclosure.

FIG. 45 is an illustration of a balloon catheter and delivery system,shown with a balloon in an inflated state, according to severalembodiments of the present disclosure.

FIG. 46 is an illustration of a balloon catheter and delivery system,shown with a balloon in a deflated state after an inflated state,according to several embodiments of the present disclosure.

FIG. 47 is an illustration of a balloon catheter and delivery systemshown withdrawing from an occlusion and with a cage-like structure in apartially deployed state, according to several embodiments of thepresent disclosure.

FIG. 48 is an illustration of a balloon catheter and delivery systemshown withdrawing from an occlusion and with a cage-like structure in afully deployed state, according to several embodiments of the presentdisclosure.

FIG. 49 is an illustration of a balloon catheter and delivery systemshown fully withdrawn and with a cage-like structure in a temporary orlong-term steady-state fully deployed state, according to severalembodiments of the present disclosure.

FIG. 50 shows a perspective view of an embodiment of a rapid reperfusiondevice in an unexpanded state.

FIG. 51 shows a perspective view of an embodiment of a rapid reperfusiondevice in an expanded state.

FIG. 52A shows a side view of an embodiment of a rapid reperfusiondevice.

FIG. 52B shows a sectional view of an embodiment of a rapid reperfusiondevice.

FIG. 52C shows a sectional view of an embodiment of a rapid reperfusiondevice.

FIG. 53A shows a side view of an embodiment of a rapid reperfusiondevice.

FIG. 53B shows a sectional view of an embodiment of a rapid reperfusiondevice.

FIG. 53C shows a sectional view of an embodiment of a rapid reperfusiondevice.

FIG. 54 shows a side view of an embodiment of a rapid reperfusion devicein an unexpanded state.

FIG. 55 shows a side view of an embodiment of a rapid reperfusion devicein an expanded state.

FIG. 56 shows a perspective view of an embodiment of a rapid reperfusiondevice in an unexpanded state.

FIG. 57 shows a perspective view of an embodiment of a rapid reperfusiondevice in an expanded state.

FIG. 58 shows a side view of an embodiment of a rapid reperfusion devicein an unexpanded state.

FIG. 59 shows a side view of an embodiment of a rapid reperfusion deviceaccording to one embodiment in an expanded state.

FIG. 60A shows a view of a rapid reperfusion device according to oneembodiment near a target embolus.

FIG. 60B shows a view of a rapid reperfusion device according to oneembodiment deployed across a target embolus.

FIG. 60C shows a view of a rapid reperfusion device according to oneembodiment deployed against a target embolus.

FIG. 61A shows a view of a rapid reperfusion device according to oneembodiment near a target embolus.

FIG. 61B shows a view of a rapid reperfusion device according to oneembodiment deployed across a target embolus.

FIG. 61C shows a view of a rapid reperfusion device according to oneembodiment deployed against a target embolus.

FIG. 61D is a side view of an embodiment of a rapid reperfusion devicecomprising an infusable microwire with an integrated filter.

FIG. 61E is a side view of an embodiment of a rapid reperfusion devicecomprising an infusable coil.

FIG. 61F is a side view of an embodiment of a rapid reperfusion devicecomprising an infusable temporary stent.

FIG. 61G is a side view of an embodiment of a rapid reperfusion devicecomprising an inflatable balloon.

FIG. 62 shows a schematic of a delivery system and an embodiment of atemporary aneurysmal treatment device mechanism.

FIG. 63 shows a temporary aneurysmal treatment device and mechanismbridging the neck of an aneurysm, according to an embodiment of theinvention.

FIG. 64 schematically depicts a delivery system with several embodimentsof an aneurysmal treatment device.

FIGS. 65 and 66 illustrate detachability of the aneurysmal treatmentdevice in accordance with an embodiment of the invention.

DETAILED DESCRIPTION I. General

Several embodiments of the invention disclosed herein provide systems,methods, and devices for the treatment of acute ischemic stroke thatprovide immediate blood flow restoration to a vessel occluded by a clotand, after reestablishing blood flow, address the clot itself. Immediateblood flow restoration to the neurovasculature distal to the clot canreduce the destruction of neurons and synapses of the brain that mayotherwise occur if the clot is attempted to be removed without firstrestoring blood flow. Immediate blood flow restoration advantageouslycan facilitate natural lysis of the clot and also can reduce or obviatethe concern for distal embolization due to fragmentation of the clot. Inaccordance with some embodiments, the clot can be addressed in-situ toreperfuse a blood vessel without occluding or blocking blood flow andwithout requiring the use of additional structures to address distalembolization.

Prior to Applicant's discoveries, accepted wisdom generally dictatedthat the thrombus should be carefully preserved so as not to disrupt ordisturb the thrombus during retrieval (to avoid embolic particles fromflowing distally and causing morbidity or mortality) and/or to employdistal embolic protection to capture any such embolic particles. Severalembodiments of the present invention are particularly unexpected becauselysis of the embolus to generate particles is enhanced, and moreover,embolic particles are allowed to be released (e.g., through macerationand/or lysis) without the need for distal embolic protection. Accordingto several embodiments of the invention, the release of embolicparticles is, surprisingly, facilitated because blood flow (which haspreviously been advantageously restored) causes lysis (e.g., enzymaticdigestion) of those particles such that the particles no longer poseissues distally.

Several embodiments of the invention provide for progressive, ormodular, treatment based upon the nature of the clot. For example, theprogressive treatment can comprise a three-step progressive treatmentprocess that includes immediate restoration of blood flow, in-situ clotmanagement, and/or clot removal depending on the particularcircumstances of the treatment (e.g., using a single expandable tipassembly or multiple expandable tip assemblies). The in-situ clotmanagement can include, for example, lysis, maceration, or both. Theprogressive, or modular, treatment can be provided by one or moretreatment devices. In some embodiments, clot removal may not benecessary due to the natural lytic destruction provided by therestoration of blood flow. In some embodiments, the progressivetreatment of flow restoration, in-situ clot management, and clot removalor capture can be performed in a matter of minutes instead of hours(e.g., less than 5 minutes, less than 10 minutes, less than 15 minutes,less than 20 minutes, less than 25 minutes, less than 30 minutes, lessthan 45 minutes). In some embodiments, a clot management system providestreating physicians with a synergistic, two-device system optimized forboth rapid reperfusion and versatile clot removal. By equipping thephysician to achieve rapid perfusion, the system can help to alleviatethe stress associated with racing against the clock to retrieve theclot.

In several embodiments, the outer layer of an embolus is removed viamaceration and/or lysis, and the inner core of the thrombus is capturedand removed. This is particularly beneficial in some embodiments becausethe outer layer particles are lysed by natural (or artificial) lytics ormechanical disruption and the inner core, which may be more adhesive,can be removed with minimal risk that any particles will slough off.Moreover, any small particles that are released can also be lysed by thelytic process. In some embodiments, about 30-80% of the thrombus islysed and about 20-70% is captured and removed.

According to some embodiments of the invention, a self-expanding device,which is microcatheter-based, can be deployed across a thrombus, therebyrestoring blood flow distal to the thrombus upon unsheathing. The devicecan then be resheathed and unsheathed one or more times to break up, ormacerate, at least a portion of the clot. The device can then remainunsheathed for a period of time in order for the device to maintainrestored flow, thereby facilitating natural lysis of the clot andallowing for incubation of the device within the clot to increaseengagement of the clot into the interior of the device (e.g., from theexterior surface). The increased engagement can facilitate removal ofthe clot (if removal is necessary). In some embodiments, clot removal isperformed while maintaining flow through or perfusion of the bloodvessel.

Various embodiments according to the present disclosure relate torevascularization systems and devices used to treat, among other things,ischemic stroke. Naturally, therefore, the revascularization systems anddevices of several embodiments of the present disclosure are designed tobe used in neuro-type applications, wherein the specifications of thepresent catheters and revascularization devices may be deployed in theblood vessels of the cerebral vascular system. For example, the systemsand devices disclosed herein can be configured to be deployed in thecerebral arteries, including but not limited to: the anterior cerebralarteries (ACA), the anterior communicating artery, the middle cerebralarteries (MCA) (including the M1 and M2 segments), the posteriorcommunicating arteries, the internal carotid arteries (ICA), thevertebral arteries, the basilar artery, and the posterior cerebralarteries (PCA). In some embodiments, the systems and devices areconfigured to be deployed in the region above the subclavian and commoncarotid arteries.

Other embodiments of the invention are not limited to theneurovasculature and may be used in other regions, including but notlimited to vessels (e.g., veins or arteries) in, to or from the heart,lungs, extremities (e.g., legs), and pelvis. Moreover, some embodimentsof the invention are not limited to vascular thrombi, but instead can bedirected to treatment (e.g., maceration, lysis, capture or combinationsthereof) of undesired targets (e.g., gallstones, kidney stones,calcifications, cysts, fibroids, tumors, etc.). Embolic debris caused byinterventions involving carotid artery stent placement and treatingsaphenous vein aortocoronary bypass grafts stenosis are treatedaccording to several embodiments described herein.

In several embodiments, a method of treating a thrombus is provided. Inone embodiment, the method first includes restoring blood flow within anoccluded vessel. To restore flow, a reperfusion device having aself-expanding scaffold at a distal end of a long pusher tube or wirecan be temporarily inserted into the occluded vessel and advanced to thelocation of the thrombus. In one embodiment, the location of thethrombus refers to a location wherein the scaffold effectively spans thethrombus (completely or substantially). Advancing the reperfusion deviceto the location of the thrombus can mean advancing the reperfusiondevice through the thrombus or to the side of the thrombus (e.g., withina microcatheter) depending on the path of least resistance and thelocation and morphology of the clot. In some embodiments, thereperfusion device is delivered through a microcatheter so that theself-expanding scaffold remains in a non-expanded configuration until adesired location is reached. The microcatheter can be pre-inserted orinserted together with the reperfusion device. The microcatheter can beadvanced to a position wherein a distal tip of the microcatheter islocated just beyond a distal end of the thrombus (e.g., within 2 cm pastthe thrombus, within 1 cm past the thrombus, within 5 mm past thethrombus, within 2 mm past the thrombus, aligned with the distal end ofthe thrombus). The reperfusion device can then be advanced within themicrocatheter until the distal end of the self-expanding scaffold isaligned with, or slightly distal to, the distal end of themicrocatheter.

The microcatheter can then be retracted proximally, thereby unsheathingthe self-expanding scaffold and allowing the self-expanding scaffold todeploy to its expanded configuration within the thrombus. Themicrocatheter and the reperfusion device can be positioned such thatwhen the self-expanding scaffold is fully deployed, it spans orsubstantially spans the thrombus. The self-expanding scaffold cancompress (e.g., impact or press against or exert radial force fromwithin) the thrombus against the vessel wall, thereby creating channelswithin or past the clot for blood to flow and facilitate clot lysis. Theself-expanding scaffold can comprise cells having a relatively smallcell size designed to minimize, hinder, prevent, deter, or reducepenetration of the thrombus, thereby maximizing the blood flow throughthe self-expanding scaffold. If the scaffold is not positioned aseffectively as desired, the microcatheter can be advanced distally toresheath the scaffold and the microcatheter and the reperfusion devicecan then be moved to a new position and redeployed.

In several embodiments, after a period of time after initial expansionof the self-expanding scaffold, the microcatheter can be advancedproximally to reconstrain and resheath the self-expanding scaffold andthen the microcatheter can be advanced distally again to redeploy thescaffold in the same position in an effort to macerate the thrombus. Theresheathing and unsheathing can be repeated one or more times. Thereperfusion device can then be removed by advancing the microcatheterdistally to resheath the scaffold and then withdrawing the reperfusiondevice from the body (with or without the microcatheter).

After a period of waiting time in which lysis is allowed to occur due tothe restored blood flow and maceration, an angiographic or other type offlow assessment can be performed. Angiographic or other flow assessmentscan be performed at any time during the treatment method (e.g., beforeor after the reperfusion device is removed). If the thrombus hascompletely lysed or lysed to a sufficient degree, the treatment may becomplete and no further steps may be necessary.

If the thrombus has not sufficiently lysed after a predetermined amountof wait time and after repeated maceration attempts, a thrombus removaldevice can be inserted into a microcatheter (which may be the samemicrocatheter as above) and advanced to the location of the remainingthrombus material within the cerebral vasculature. The thrombus removaldevice can be deployed in a similar manner as described above withrespect to the reperfusion device. The thrombus removal device caninclude a self-expanding scaffold at a distal end of a long pusher tubeor wire similar to the reperfusion device. In one embodiment, theself-expanding scaffold of the thrombus removal device can include cellshaving a relatively large cell size compared to the reperfusion devicedesigned to maximize, increase, facilitate, aid, encourage, enhance,promote, or allow penetration of the remaining thrombus material,thereby increasing the likelihood of engagement with and capture of theremaining thrombus material.

In some embodiments, the thrombus removal device can be resheathed andredeployed one or more times to increase the likelihood of engagementwith and capture of the remaining thrombus material. The thrombusremoval device (along with the captured thrombus material) can then bewithdrawn from the blood vessel. In some embodiments, the microcatheteris advanced distally to resheath the self-expanding scaffold of thethrombus removal device before being withdrawn. In other embodiments,the self-expanding scaffold remains in its deployed configuration andthe microcatheter and the thrombus removal device are withdrawnproximally into a larger guide catheter.

FIG. 1 illustrates a representation of the anatomy of the cerebralvasculature of a human from an anterior view. With reference to onehemisphere of the brain, the cerebral vasculature includes an anteriorcerebral artery 10, a middle cerebral artery 20, an internal carotidartery 30 and a posterior cerebral artery 40. FIG. 1 also illustrates abasilar artery 50 and a vertebral artery 60. Occlusions or blockagewithin these arteries can prevent blood flow to the brain, therebyresulting in ischemic stroke.

In accordance with some embodiments, the systems, methods, and devicesdisclosed herein are used in a patient's neurovasculature in order totreat intracranial atherosclerotic disease (ICAD) or to treat aneurysmsby providing an aneurysm neck bridge. Treatment of aneurysms isdescribed in more detail herein and is also described in U.S.Publication No. 2009/0125053 filed on Jun. 10, 2008, the entire contentof which is hereby expressly incorporated by reference herein. Similarlycontemplated for the revascularization systems and devices of thepresent disclosure is deployment in other parts of the body wherein thespecifications of the present disclosure may be used in other vessels orlumens of the body in a minimally invasive or non-invasive manner.

In accordance with some embodiments, the systems, methods and devicesdisclosed herein provide ease of use, increased effectiveness, andenhanced safety over existing systems, methods and devices. For example,in embodiments incorporating deployment over a guidewire, the systemscan provide enhanced trackability and maintained access to the treatmentsite during the treatment procedures. If multiple treatment devices areto be used, the guidewire can remain in place to maintain access,thereby decreasing the complexity and time of the overall clot therapytreatment. In some embodiments, multiple passes are not required toremove the clot; instead the clot can be removed in a single pass.

In accordance with some embodiments, large distal embolic fragments arenot created, thereby preventing a need for distal embolic protection. Insome embodiments, blood flow is not occluded, restricted, or obstructedduring reperfusion, in-situ clot management, and/or clot removal.

In some embodiments, relatively small embolic fragments are produced asa result of maceration without concern for distal embolization based inpart on the new and surprising discovery that distal embolization is nota concern when a blood vessel is first reperfused and blood flow isrestored. Early blood flow restoration can provide new blood to thestunned ischemic region that is distal to the occlusive thrombus. Thenew blood can transport plasminogen activators and plasminogen to thethrombus surface. In accordance with some embodiments, after new bloodhas penetrated distal to the thrombus, if emboli is created as a resultof thrombectomy, the emboli will lyse via enzymatic digestion ratherthan becoming a new occlusive thrombus requiring additional lysis.

In accordance with some embodiments, the systems and devices do notrequire an actuator that requires mechanical actuation or manipulationto effect deployment and retraction. For example, the systems anddevices disclosed herein can be configured to provide automaticexpansion without mechanical actuation using self-expanding devices thatallow the devices to self-conform, self-adjust, or self-regulate to anysize lumen or vessel. The self-conforming feature prevents or reducesthe likelihood of overexpansion, thereby improving safety, and reducescomplexity of the structure and operation of the systems and devices.

The systems, methods and devices described herein can provide increasedeffectiveness. Some embodiments of the invention advantageously providefor immediate restoration of blood flow. The immediate restoration ofblood flow advantageously can facilitate natural lysis of the clot and,even if complete lysis does not occur, results in the clot being alteredto be more manageable, thereby facilitating effective removal. As usedherein, the term “immediate” as used herein shall be given its ordinarymeaning and shall also include a designated action or result that occursin less than about 10 seconds, less than about 30 seconds, less thanabout one or two minutes, less than about five minutes, less than aboutten minutes, less than about twenty minutes, or less than about thirtyminutes. In some embodiments, the term immediate can mean that adesignated action occurs in a matter of seconds or minutes rather thanin a matter of hours. In one embodiment, blood flow is restoredimmediately (e.g., within about 1 to 2 minutes) upon placement of thedevice in the neurovasculature. In one embodiment, blood flow isrestored immediately (e.g., within about 5-30 minutes) upon initialinsertion of the device into a patient (e.g., into the femoral artery).In several embodiments, blood flow is restored according to severalembodiments of the invention in less than about half the time it wouldtake for other devices to restore flow. In other embodiments, blood flowis restored according to several embodiments of the invention in lessthan about ¼, ⅕, or 1/10 time it would take for other devices to restoreflow.

In some embodiments, the systems, methods, and devices disclosed hereinreduce the time required to restore blood flow through an occludedvessel. In accordance with some embodiments, the systems, methods anddevices provide restored blood flow in an amount of time that is atleast thirty seconds less than existing systems, methods and devices. Insome embodiments, the time from initial puncture of the skin to beginthe delivery procedure to initial restoration of normal flow is betweenthirty seconds and thirty minutes (e.g., between thirty seconds and fiveminutes, between one minute and three minutes, between five minutes andten minutes, between five minutes and fifteen minutes, between tenminutes and twenty minutes, between fifteen minutes and thirty minutes,or overlapping ranges thereof).

According to scientific estimates based on studies of large vessel,supratentorial ischemic strokes, every minute of occluded flow resultsin the loss of approximately 1.9 million neurons and 14 billion synapsesand every second of occluded flow results in the loss of approximately32,000 neurons and 230 million synapses. See Jeffrey Saver, “Time isBrain—Quantified,” Stroke, volume 37, pages 233-236 (2006). Accordingly,even a thirty-second reduction in the time required for blood flowrestoration is significant. Several embodiments of the systems, methodsand devices described herein provide increased flow rates (e.g.,Thrombolysis in Myocardial Infarction or TIMI scores) in shorter timethan current systems and improved modified Rankin scores more frequentlyand in shorter time than current systems.

The systems, methods and devices described herein can provide enhancedsafety. For example, according to several embodiments, the inventionprovides one or more of the following advantages: reduced vesselperforation or dissection, lower hemorrhage rate, less distalembolization, and lower death rates. In some embodiments, the inventioncomprises an expandable scaffold to be deployed, resheathed, andre-deployed in-situ without significant risk of damage to the vesselbecause the expandable scaffold is not moved laterally within the vesselwhile in its expanded configuration. In some embodiments, the expandablescaffolds described herein include a tapered (e.g., angled) proximal endhaving an everted or scooped-out (e.g., open) portal or mouth thatreduces the likelihood of vessel damage (e.g., vessel perforation,vessel dissection, endothelial disruption) when the expandable scaffoldis being recaptured or resheathed within a microcatheter.

II. Terminology

As used herein, the terms “treat,” “treatment” and “treating” shall begiven their ordinary meaning and shall refer to therapy, management,preventive care, repair, assessment, removal, and/or the like. Withparticular reference to stroke treatment, the terms can refer to thereduction or amelioration of the progression, severity, and/or durationof a stroke or a symptom thereof. Treatment as used herein withreference to stroke treatment includes, but is not limited to,decreasing the size or firmness of a clot, removing a clot, increasingblood flow, increasing cerebral perfusion, facilitating natural lysis ofa clot, macerating a clot, repairing aneurysms, reducing destruction ofbrain synapses, improving modified Rankin scores, and improving brainfunction.

The term “scaffold” as used herein shall be given its ordinary meaningand shall include, without limitation, support members, collapsiblemembers, expandable members, distensible members, reconstrainablemembers, solid structures, mesh structures, braided structures, wovenstructures, porous structures, open-cell structures, closed-cellstructures, struts, stents, baskets, polymeric structures, membranes,bladders, umbrella-type devices, ribs, spokes, frames, and the like, andcombinations thereof. Scaffolds may be fully or partially covered or maybe uncovered. Covered scaffolds may comprise skeletons that arepartially or fully covered by membranes, fabrics, films, multiplelayers, and/or coated. Scaffolds may be mechanically actuated,self-actuated, inflated, and/or combinations thereof.

As used herein, the terms “reperfusion,” “recanalization,”“revascularization”, and their derivatives shall be given their ordinarymeanings and can refer to restoration of blood flow or blood supply. Theterms reperfusion, recanalization, and revascularization can refer tothe creation of a bypass from the patent vessel to beyond the occlusivethrombus. The terms are used interchangeably throughout the disclosure.

The terms “clot,” “thrombus,” or embolus” as used herein can be usedinterchangeably and shall be given their ordinary meanings and can referto any occlusion or obstruction of a blood vessel. The terms can referto a body of biological material or a foreign, non-biological material.

The terms “lysis,” “lytic” and their derivatives as used herein shall begiven their ordinary meanings and can refer to natural lysis (e.g., dueto restored blood flow), mechanical lysis (e.g., due to contact orpressure), or chemical lysis (e.g., thrombolysis due to lytic agentsand/or enzymatic digestion). Natural lysis due to restored blood flowcan occur due to natural lytic compounds found in the blood (e.g.,enzymes) and/or to the shear force of the flow. In some embodiments,lysis refers to any biological or other cellular or sub-cellular processor result of altering the structure of a clot. Lysis may refer tofibrinolysis—degradation of fibrin—within a fibrin clot by applicationof enzymes. For example, lysis may occur in the presence of plasmin,heparin, etc.; precursors or activation peptides thereof; or inhibitorsof fibrin development. Lysis includes partially or fully dissolving orshrinking a thrombus (or embolic particles released from a thrombus).Lysis can be considered sufficient if the thrombus is lysed (e.g.,dissolved, broken up into pieces, or shrunk) such that the thrombus nolonger presents a risk of further occlusion or blockage of blood flow.

The term “maceration” and its derivatives as used herein shall be giventheir ordinary meanings and can refer to the process or result ofsoftening of the clot or breaking the same into pieces mechanically orby using vascular fluids. Macerating can refer to pressing, compressing,diffusing, dissolving, disrupting, fragmenting, obliterating,destroying, breaking up, imploding, and/or softening. For example,pressing or compressing the clot with a mechanical member can cause theclot to soften, break up or fragment, whereby, exposure of the clot (orportions thereof) to vascular flow may cause the clot (or portionsthereof) to fragment, soften, or diffuse.

The term “removal” and its derivates as used herein shall be given theirordinary meaning and can refer to capture and extraction from apatient's body or engagement and relocation of material or portions ofthe material, to a different region of the body. In some embodiments,“removal” can refer to destruction or reduction in size or content andnot extraction in toto, or as a whole.

III. Clot Management Systems

A. General Systems

According to several embodiments, disclosed herein are catheter-basedrevascularization systems (e.g., clot management systems, stroketreatment systems). In accordance with some embodiments, therevascularization systems described herein comprise one or moreexpandable tip microcatheter assemblies that are configured to betemporarily inserted into cerebral vasculature of patients experiencingan acute ischemic stroke.

A catheter-based revascularization system effective for delivering aneurological medical device into a desired location in the cerebralvascular system is provided according to several embodiments. Therevascularization system (e.g., stroke treatment system, clot managementsystem) can function in at least three respective modes for addressing aclot: a reperfusion/blood restoration mode, a clot management mode, anda clot removal mode. The clot management mode can include macerationand/or lysis of the clot.

The revascularization systems (e.g., stroke treatment systems, clotmanagement systems) can comprise two-part systems wherein blood flow isfirst restored and then an occlusion is removed, rather than justremoving the occlusion without first reperfusing the vessel. Inaccordance with some embodiments, the revascularization systems providelysis and maceration in situ before removal of the clot. In someembodiments, the in situ lysis and maceration can result in moreeffective removal of the clot. For example, the clot morphology can beimproved by the lysis and maceration (e.g., reduced clot size or removalof soft, rubbery portions that make the clot difficult to grasp andremove). In some embodiments, the revascularization systems, or at leastcomponents of the systems, are configured for single use only and aredisposable.

According to some embodiments, deployment of the systems disclosedherein increases the diameter of the flow channel and/or the flow ratethrough the blocked vessel by at least about 25%, 50%, 75% or more. Insome embodiments, the systems have an adequately small profile withflexibility to promote improved access for in-site treatment is knownwhich may be used as a temporary (e.g., not implanted) solution.

According to several embodiments and as illustrated in FIG. 2A, acatheter-based revascularization system 100 provides a platform forlysing emboli in occluded blood vessels. Accordingly, the catheter-basedrevascularization system 100 generally comprises a control end 102 and adeployment end 104. In one embodiment, control end 102 is a portion ofthe device that allows a user, such as a surgeon, to control deploymentof the device through the blood vessels of a patient. Included as partof the control end 102 is a delivery handle 106 and a winged apparatus108, in some embodiments. Control end 102 can include a Tuohy Borstadapter and one or more rotating hemostasis valves. In some embodiments,module 113 (see FIG. 2B) is detachable.

According to some embodiments of systems, during shipping of thecatheter-revascularization system 100, shipping lock (not shown) isinstalled between the delivery handle 106 and the winged apparatus 108to prevent deployment and premature extension of a revascularizationdevice 124 (see FIG. 2B) while not in use. Furthermore, by preventingthe delivery handle 106 from being advanced towards the winged apparatus108, coatings applied to the revascularization device 124 are stored ina configuration whereby they will not rub off or be otherwise damagedwhile the catheter-based revascularization system 100 is not in use.

According to several embodiments, an agent delivery device 130 providesa conduit in fluid communication with the lumen of the catheter-basedrevascularization system 100 enabling users of the system to deliveragents (e.g., lytic agents, clot adhesion agents) through catheter-basedrevascularization system 100 directly to the location of the embolus.The revascularization system delivery device (e.g., distal segment 120of FIG. 1B) may be made from materials known to artisans, includingstainless steel hypotube, stainless steel coil, polymer jackets (e.g.,polymeric liners), and/or radiopaque jackets (e.g., markers or bands).

A luer connector 132 or a functional equivalent can provide sterileaccess to the lumen of the catheter-based revascularization system 100to effect delivery of a chosen agent. The agent can include, but is notlimited to, lytic agents, blood-thinning agents, and compounds oradherents formulated to promote clot adhesion or platelet activation. Anexample of an embodiment of a luer connector that can be used with thesystems described herein is described in U.S. Patent Publication No.2010/022951 filed May 20, 2009, the entirety of which is incorporated byreference herein.

Deployment end 104 of the catheter-based revascularization system 100comprises a proximal segment 110 and a distal segment 120. The proximalsegment 110, according to several embodiments, houses the distal segment120 and comprises an outer catheter 112 (e.g., a microcatheter) that isof a suitable length and diameter for deployment into the blood vesselof the neck, head, and cerebral vasculature.

Referring also to FIG. 2B, distal segment 120 (e.g., an expandable tipassembly or expandable stroke treatment device) comprises an innercatheter 122 (e.g., an elongate member having a lumen) and arevascularization device 124 (e.g., an expandable scaffold)—as shownhere in one embodiment having uniform cells, variable cells likewisebeing within other embodiments—which is connected to the inner catheter122. The inner catheter 122, according to several embodiments, is madefrom coil, wire, or ribbon or laser cut hypotube and is of a suitablelength and diameter to move through the outer catheter 112 duringdeployment. In some embodiments, the inner catheter 122 comprisesstainless steel or any other metallic, alloy-based, or polymericmaterial.

In accordance with some embodiments, the revascularization systems(e.g., stroke treatment systems) include a guide catheter, an outercatheter (e.g., a microcatheter), one or more guidewires and/or one ormore stroke treatment devices (e.g., recanalization devices,revascularization devices, reperfusion devices, expandable tipassemblies). In some embodiments, one or more stroke treatment devices(e.g., expandable tip assemblies) can be provided in a kit andappropriately-sized off-the-shelf or conventional guide catheters,microcatheters and guidewires can be used at the discretion of aclinician to effect delivery of a selected one or more of the stroketreatment devices (e.g., expandable tip assemblies) to target treatmentlocations. The kit of stroke treatment devices can include reperfusiondevices designed and configured to provide immediate blood flowrestoration and removal devices designed and configured to facilitateeffective clot removal.

With reference to FIG. 3, an embodiment of a revascularization system300 (e.g., clot management system, stroke treatment system) isillustrated within an occluded vessel 305. The revascularization system300 includes a guide catheter 310, a microcatheter 315, a guidewire 320,and an expandable tip assembly 325. The expandable tip assembly 325(e.g., stroke treatment device) is shown in its deployed configurationwithin an occlusion 330 during an embodiment of a revascularizationprocess (e.g., clot management process illustrated in FIGS. 33A-33F). Insome embodiments, the revascularization system 300 does not include oneor more of the above-recited components. With reference to FIG. 3A, insome embodiments, the revascularization system 300 includes a neurodistal access catheter 312.

1. Guide Catheter

In some embodiments, the guide catheter 310 accesses a blood vesselunder standard interventional procedures (e.g., using an endovascular orpercutaneous approach via an incision in a femoral artery and/or usingthe Seldinger technique). The guide catheter 310 can have an innerdiameter large enough to receive a microcatheter and still allow forcontrast injection while the microcatheter is in place, therebyadvantageously allowing for fluoroscopic road mapping during theprocedures. In some embodiments, the guide catheter 310 has an innerdiameter of at least 0.056 inches; however, inner diameters between0.030 inches and 0.090 inches, between 0.040 inches and 0.085 inches,between 0.050 inches and 0.080 inches, less than 0.020 inches, greaterthan 0.090 inches, or overlapping ranges thereof can be used. In someembodiments, the guide catheter 310 comprises a balloon guide catheterhaving a balloon 311 configured to temporarily obstruct flow (partiallyor completely) during removal of an occlusion (e.g., clot or foreignbody). In some embodiments, the guide catheter 310 is aspirated (e.g.,with a syringe) during removal of an occlusion. The guide catheter 310can comprise a 6 French (F) or larger guide catheter; however guidecatheters of larger or smaller diameters can be used as desired and/orrequired. In some embodiments, the inner diameter of the guide catheteris 7 F (0.059 inches), 8 F (0.078 inches) or 9 F (0.085 inches). Theguide catheter can comprise a neuro guide catheter having a length of 90cm, 100 cm, less than 90 cm, or greater than 100 cm.

2. Distal Access Catheter

With reference to FIG. 3A, in some embodiments, the revascularizationsystem, or stroke treatment system, 300 comprises a neuro distal accesscatheter 312 configured to be inserted within a guide catheter (e.g.,guide catheter 310) and a microcatheter (e.g., microcatheter 315) isconfigured to be inserted within the distal access catheter 312. Theterm “distal access catheter” as used herein shall be given its ordinarymeaning and shall also include distal support catheters and/oraspiration catheters. In some embodiments, the guide catheter 310 isconfigured to provide proximal aspiration (e.g., aspiration within anupstream artery proximal to an occluded downstream artery and remotefrom the thrombus or clot) and the distal access catheter 312 (e.g.,distal aspiration and/or aspiration catheter) is configured to providelocal aspiration (e.g., aspiration at a location proximal to and inclose proximity to the thrombus or clot but within the occluded artery).For example, the distal access catheter 312 can be a thrombus-aspirationcatheter and a syringe, needle, vacuum, or other aspiration device canbe connected, attached or otherwise coupled to, or inserted within, aproximal end (e.g., end outside the body) of the distal access catheter312. The aspiration can be provided by manual aspiration or automaticaspiration devices and/or methods.

In some embodiments, local aspiration at or in close proximity to thelocation of the thrombus provided by the distal access catheter 312(e.g., distal support and/or aspiration catheter) advantageouslyincreases the likelihood of, or facilitates, capture or removal ofportions of the thrombus as the expandable tip assembly. In someembodiments, the local aspiration increases the likelihood of, orfacilitates, capture or removal of a core of the thrombus. In someembodiments, the distal access catheter 312 is a distal support catheterthat provides increased arterial and/or microcatheter support andfacilitates access to the occluded vessel (e.g., cerebral arteries) overthe microcatheter 315 alone. In some embodiments, the distal accesscatheter 312 (e.g., distal support and/or aspiration catheter) providesarterial and/or microcatheter support distal to the distal end of theguide catheter 310. In some embodiments, the distal access catheter 312adjusts a direction of the force on the thrombus during removal tosubstantially align with a longitudinal axis of the blood vessel,thereby increasing the likelihood of successful removal of the thrombus.

In some embodiments, the distal access catheter 312 has an outerdiameter that is less than the inner diameter of the guide catheter 310and an inner diameter that is greater than the outer diameter of themicrocatheter 315. In some embodiments the outer diameter is between 4 Fand 8 F (e.g., between 4 F and 7 F, between 5 F and 8 F, between 5 F and7 F and overlapping ranges thereof) and the inner diameter is between0.030 inches and 0.070 inches (e.g., between 0.030 inches and 0.050inches, between 0.040 inches and 0.070 inches, between 0.050 inches and0.060 inches, or overlapping ranges thereof). In one embodiment, thedistal access catheter 312 is a 6 F catheter having an inner diameter of0.057 inches. In some embodiments, the inner diameter of the distalaccess catheter 312 is greater than the outer diameter of the guidecatheter 310. In some embodiments, the distal access catheter 312 isused instead of the guide catheter 310. In some embodiments, the distalaccess catheter 312 is used instead of the microcatheter 315. In someembodiments, the larger diameter of the distal access catheter 312allows for more effective aspiration than if aspiration were performedthrough the microcatheter 315 alone.

In some embodiments, the distal access catheter 312 can slow down bloodflow but not totally occlude flow (e.g., through aspiration). In someembodiments, the distal access catheter 312 comprises a balloon. In someembodiments, the distal access catheter 312 comprises one or morelumens. In one embodiment, the distal access catheter 312 comprises asingle central lumen. In some embodiments, the distal access catheter312 comprises multiple holes at its distal or proximal ends tofacilitate increased aspiration and to reduce the likelihood ofblockage.

In one embodiment of a method of managing blood clots inneurovasculature, the balloon guide catheter 310 is inserted into thebody and a distal end of the guide catheter 310 is advanced to thecerebral vasculature proximal or downstream of an occluded artery (e.g,to the common carotid artery or proximal segment of the ICA for MCAocclusions or to an origin of one of the vertebral arteries for basilarartery occlusions). The distal access catheter 312 can then be insertedwithin a lumen of the guide catheter 310 and a distal end of the distalaccess catheter 312 can be advanced to a location adjacent an occlusion(e.g., clot, thrombus, embolus) within an occluded artery (e.g., withinan MCA or at the bifurcation between the ICA and the MCA for MCAocclusions or within the basilar artery or a proximal segment of avertebral artery for basilar occlusions). In some embodiments, a distalend of the distal access catheter 312 can be positioned at an origin ofan occluded artery or other blood vessel. The microcatheter 315 can thenbe inserted through a lumen of the distal access catheter 312 and adistal end of the microcatheter 315 can be positioned at a location thatcoincides with the occlusion (e.g., clot, thrombus, embolus). Theexpandable tip assembly 325 can then be inserted through a lumen of themicrocatheter 315 and advanced to the distal end of the microcatheter315. The microcatheter 315 can then be retracted proximally as describedin more detail in connection with FIGS. 33A-33F to cause the expandabletip assembly 325 to be deployed in a manner that at least partiallyspans the occlusion (e.g., clot, thrombus, embolus).

In some embodiments, the distal access catheter 312 can provide localaspiration (e.g., aspiration in close proximity to a thrombus or otherocclusion). The distal end of the distal access catheter 312 can bepositioned between 10 mm and 10 cm of the thrombus or a proximal end ofthe expandable tip assembly 325 (e.g., between 10 mm and 30 mm, between20 mm and 50 mm, between 30 mm and 80 mm, between 40 mm and 100 mm, oroverlapping ranges thereto). In some embodiments, the distal end of thedistal access catheter 312 is positioned less than 10 mm from thethrombus or a proximal end of the expandable tip assembly 325 or greaterthan 10 cm from the thrombus or a proximal end of the expandable tipassembly 325.

As described in more detail herein, the expandable tip assembly 325 canrestore blood flow through an occluded vessel and the natural lyticaction of the restored blood flow can lyse thrombus or embolus materialwithin the neurovasculature. The expandable tip assembly 325 can also beconfigured to engage and capture at least a portion of a thrombus orother occlusive object within the occluded artery and remove theocclusive object upon removal of the expandable tip assembly 325.

In several embodiments, the expandable tip assembly 325, themicrocatheter 315, the guide catheter 310 and the distal access catheter312 are removed from the patient after the thrombus or other occlusiveobject has been treated, managed, or otherwise addressed and blood flowhas been restored. In some embodiments, the distal access catheter 312is removed from the patient simultaneously with the expandable tipassembly 325, microcatheter 315 and the guide catheter 310. In otherembodiments, the distal access catheter 312 is removed from the patientbefore or after the expandable tip assembly 325, microcatheter 315and/or the guide catheter 310.

3. Microcatheter

In some embodiments, the microcatheter 315 is configured to receive,house, deliver, and remove the expandable tip assembly 325. Themicrocatheter 315 can be configured to provide a sheathing function forthe expandable tip assembly 325. In some embodiments, the expandable tipassembly 325 can be inserted within the microcatheter 315 in acompressed, or non-expanded, configuration and advanced to a distal endof the microcatheter 315. The microcatheter 315 can then be retractedproximally with respect to the expandable tip assembly 325 to allow theexpandable tip assembly 325 to transition to a deployed, or expanded,configuration at least a portion thereof having a diameter greater thanin the unexpanded configuration. The microcatheter 315 can comprise aconventional microcatheter selected by a particular medical professionalor clinician (e.g., due to familiarity, ease of use, or cost) or aproprietary microcatheter that is provided in a kit together with one ormore expandable tip assemblies.

According to several embodiments, the microcatheter length and diameterare suitable for inserting into a human patient and capable of reachinga target embolus in the region above the subclavian and common carotidarteries while still being accessible to a clinician from outside apatient's body. For example, according to several embodiments, themicrocatheter 315 is between about 135 cm and about 175 cm long, betweenabout 135 cm and about 150 cm, between about 140 cm and about 150 cm,shorter than 135 cm, longer than 175 cm, or overlapping ranges thereof.In various alternative embodiments, the microcatheter 315 has a lengthof 90 cm, 100 cm, 115 cm, 125 cm, 130 cm, 135 cm, 136 cm, 140 cm, or 150cm. The microcatheter 315 can comprise a neuro microcatheter.

The microcatheter 315 includes a proximal segment (at a control end ofthe microcatheter) and a distal segment (at a deployment end of themicrocatheter). In some embodiments, the proximal segment is about 115cm long with an outer diameter of between about 2.0 F and 3.5 F (e.g.,2.5 F, 2.8 F, 3.5 F) and the distal segment is about 35 cm with an outerdiameter of between about 1.5 F and 3.0 F (e.g., 1.7 F, 1.9 F, 2.3 F 2.5F, 2.8 F); however the proximal segment can be from 75 cm to 150 cmlong, from 100 cm to 130 cm long, from 90 cm to 120 cm long, shorterthan 75 cm, longer than 150 cm, or overlapping ranges thereof and havean outer diameter between about 1.5 F and 3.7 F, between about 3.0 F and4.0 F, between about 2.5 F and 3.5 F, less than 1.5 F, greater than 4.0F, or overlapping ranges thereof. The distal segment can be betweenabout 20 cm and 40 cm long, between about 25 cm and 50 cm long, betweenabout 30 cm and 40 cm long, shorter than 20 cm, longer than 50 cm, oroverlapping ranges thereof and have an outer diameter between about 1.0F and 3.0 F, between about 1.5 F and 3.5 F, between about 1.5 F and 2.5F, less than 1.0 F, greater than 3.5 F, or overlapping ranges thereof.

According to some embodiments, a gradual decrease or stepwise in theouter diameter dimension of the microcatheter 315 as a function of thedistal distance from the proximal segment. For example, the proximalsegment can be 3.5 F at the most proximal end and the distal segment canbe 2.7 F at the most distal end. As another example, the proximalsegment can be 2.7 F at the most proximal end and 1.7 F at the mostdistal end. Disposed between is an intermediate segment having one ormore intermediate outer diameters between the maximum and minimumdiameters. For example, for a microcatheter with a maximum diameter atthe proximal end of 3.5 F and a minimum diameter at the distal end of2.7 F, the intermediate outer diameters can comprise 3.4 F, 3.3 F, 3.2F, 3.1 F, 3.0 F, 2.9 F, and 2.8 F. For a microcatheter with a maximumdiameter at the proximal end of 2.7 F and a minimum diameter at thedistal end of 1.7 F, the intermediate outer diameters can comprise 2.5F, 2.4 F, 2.3 F, 2.2 F, 2.1 F, 2.0 F, 1.9 F, and 1.8 F.

The inner diameter of microcatheter 315 can range from 0.010 inches to0.020 inches, from 0.015 inches to 0.030 inches (e.g., 0.0165 inches,0.017, inches, 0.021 inches, 0.025 inches, 0.027 inches), less than0.010 inches, greater than 0.030 inches, or overlapping ranges thereof,which can allow the microcatheter 315 to be inserted along a preinsertedguidewire or used to infuse therapeutic agents. The inner diameter canbe reduced to a size that still allows for infusion when an expandabletip assembly or other device is in place within the microcatheter. Insome embodiments, infusion capabilities can be sacrificed and the innerdiameter can be reduced to a size as small as material properties (e.g.,Young's modulus) will allow. According to several embodiments, theperformance of the microcatheter 315 is comparable to standardmicrocatheters and is designed to track over a guidewire through theneurovasculature.

4. Expandable Tip Assembly

In some embodiments, the revascularization systems, or stroke treatmentsystems, comprise an acute stroke recanalization device, an acute strokerevascularization device, a reperfusion device, or a clot removaldevice. The acute stroke recanalization devices, the acute strokerevascularization devices, the reperfusion devices, and the clot removaldevices shall generally be referred to herein as expandable tipassemblies. The expandable tip assembly 325 can comprise an elongatemember and an active segment (e.g., an expandable scaffold). In someembodiments, the elongate member comprises a generally tubular memberhaving a lumen. The expandable scaffold can be coupled to a distal endof the elongate member. In some embodiments, the expandable scaffold ispermanently or detachably tethered (e.g., coupled, attached, connected)to a distal end of the elongate member via tether wires or one or moreother tethering members. In some embodiments, the expandable scaffold isa temporary device that is tethered or coupled to the elongate memberduring the entire procedure (e.g., not releasably or detachably tetheredand not designed to be, configured to be, or capable of being, detached,released or implanted). In other embodiments, the expandable scaffoldcan be detached and left in place within a vessel on a long-term orpermanent basis.

The expandable scaffold can comprise a self-expanding scaffold, amechanically expandable scaffold, or a balloon inflatable scaffold. Theexpandable scaffold can be configured to transition between acompressed, or non-expanded, configuration or state and a deployed, orexpanded, configuration or state. At least a portion of the scaffold hasa greater diameter in the expanded configuration than in thenon-expanded configuration. In some embodiments, the expandable scaffoldis reconstrainable. In accordance with some embodiments, an expandabletip assembly can be sized and configured to be inserted within andlongitudinally movable within the microcatheter, which can act as asheath to maintain the expandable scaffold in its compressedconfiguration. Upon retraction of the microcatheter, the expandablescaffold can be deployed to its expanded configuration within a bloodvessel. Embodiments of expandable tip assemblies will be described inmore detail below.

5. Guidewire

The revascularization systems (e.g., stroke treatment systems) describedherein, or components thereof, can be configured to be deployed over oneor more guidewires. In some embodiments, a guidewire (e.g., guidewire320) is inserted into a vessel via a guide catheter and advanced througha clot. In some embodiments, a microcatheter and an expandable tipassembly are advanced over the one or more guidewires to the location ofthe clot; however, in other embodiments, only the expandable tipassembly is advanced over a guidewire. In some embodiments, the elongatemembers of the expandable tip assemblies comprise a guidewire lumenconfigured to receive the guidewire. In some embodiments, leaving theguidewire in place after deployment of an expandable tip assembly incurved vessels might be an option to stabilize the expandable tipassembly and thus prevent displacement. The guidewire advantageously canbe left in place to maintain access to a target location when multipledevices are inserted and removed in succession during a treatmentprocedure.

In some embodiments, at least a portion of the guidewire advantageouslycan comprise soft, flexible material that can flex to traverse tortuousor curved vessels. In some embodiments, the guidewire comprises acoating to facilitate insertion and removal (e.g., to reduce friction)through lumens of a microcatheter and/or expandable tip assemblies.

In some embodiments, the guidewire comprises a standard off-the-shelfneuro guidewire having a maximum diameter of between 0.005 inches and0.015 inches (e.g., 0.010 inches, 0.011 inches, 0.012 inches, 0.013inches, 0.014 inches, 0.015 inches, 0.009 inches, 0.008 inches, 0.007inches, 0.006 inches, 0.005 inches). The guidewire can have a usablelength that is at least greater than the length of the expandable tipassembly. In some embodiments, the guidewire has a usable length ofbetween 165 cm and 350 cm, between 175 cm and 215 cm, between 200 cm and310 cm, 180 cm, 205 cm, 300 cm, less than 165 cm, greater than 350 cm,or overlapping ranges thereof. In some embodiments, therevascularization system (e.g., stroke treatment system) does notinclude a separate guidewire configured to be received by a lumen of anelongate member of an expandable tip assembly.

B. Multiple Device Modular System

In some embodiments, the revascularization systems (e.g., stroketreatment systems, clot management systems) comprise a kit of expandabletip assemblies (e.g., stroke treatment devices, reperfusion devices,clot removal devices) configured to provide a poly-modic, or modular,system of separate individual devices that can be selected by aclinician depending on the circumstances of the situation, therebyproviding progressive therapy or treatment. The modular system providedby the kit of individual devices increases the number of optionsavailable to the medical professional during treatment and facilitatesaccess to vessels of different sizes, thereby allowing the medicalprofessional to adapt the stroke treatment in real time based onparticular patient or clot characteristics. In some embodiments, themodular system can be iterated to impact, address and/or cross anembolus, radially filter, and/or remove the offending embolus or beoptionally emplaced to address the same.

For example, multiple expandable tip assemblies (e.g., stroke treatmentdevices) having varying characteristics and properties to accommodatediffering vessel sizes and to address variable clot morphology can beincluded as a kit. The kit of multiple treatment devices advantageouslycan allow a clinician to select the device or sequence of devices thathave the best chance of restoring flow the fastest and/or removing theobstruction most effectively. The kit of multiple treatment devicesallow for access to all treatable vessels of the cerebral vasculature.In some embodiments, the clinician can select the best device dependingon anatomic location and blood clot morphology. In accordance with someembodiments, the clinician can adjust the treatment to addressparticular circumstances (e.g., patient characteristics, clotcharacteristics, time restrictions, vessel diameters, success of priortreatment steps, etc.) in a progressive, modular fashion. In someembodiments, all of the treatment devices can be delivered over the sameguidewire and within the same microcatheter.

In some embodiments, the multiple treatment devices comprise expandabletip assemblies. The expandable tip assemblies can be sized andconfigured for specific vessel diameters. In some embodiments, theexpandable tip assemblies can include mechanical properties and designfeatures configured to address or enhance particular treatment options(e.g., different cell sizes, hoop strengths, strut thicknesses orwidths, radial resistive forces, chronic outward forces, exteriorsurface finishes). For example, one or more expandable tip assemblies(e.g., reperfusion devices) can be configured to provide therapeuticallyeffective reperfusion and/or maceration of a clot (e.g., relativelysmall cell size, increased radial strength, and a polished exteriorsurface). Other expandable tip assemblies (e.g., clot removal or clotcapture devices) can be configured to provide effective engagement andremoval of a clot (e.g., relatively large cells that resist deformationand a rough exterior surface). In accordance with some embodiments, someof the expandable tip assemblies can be configured to treat soft clotsand some of the expandable tip assemblies can be configured to treatfirm clots. For example, the expandable tip assemblies configured totreat soft clots can be configured to gently massage the clot and theexpandable tip assemblies configured to treat firm clots can comprise arelatively stiff structure that resists cell deformation. Celldeformation can refer to the decrease in the area of the cell opening.

C. Single Device Systems

In some embodiments, the revascularization systems (e.g., stroketreatment systems, clot managements systems) comprise a single deviceconfigured to address variable clot morphologies and/or provide varioustreatment effects. For example, a single device can comprise variablemechanical structural features or designs (e.g., cell size, chronicoutward force, strut thickness, and/or other scaffold parameters orcharacteristics described herein), that allow a single device to provideeffective blood flow restoration, in-situ clot management (e.g.,maceration), and/or effective clot removal. In some embodiments, asingle device can be configured to address and/or treat both hard andsoft clots. In some embodiments, as shown in FIG. 4, an expandablescaffold 400 comprises variable cell sizes at different portions of theexpandable scaffold 400. The portions of the expandable scaffold 400having relatively small cell sizes can be configured to provide orfacilitate effective blood flow restoration or reperfusion and theportions of the expandable scaffold 400 having relatively large cellsizes can be configured to provide or facilitate effective clot removal.

With reference to FIG. 5, an expandable scaffold 500 can comprise areperfusion portion 502 configured to provide effective reperfusion of ablood vessel and a removal portion 504 configured to provide effectiveclot removal. The reperfusion portion 502 can comprise an intertwinedtight lattice structure (e.g., mesh, struts, wires) having a very smallcell size and the removal portion 504 can comprise large, open cellsconfigured to facilitate penetration, or protrusion, into, and adhesionof the clot to, the expandable scaffold 500 (e.g., exterior surfaces ofthe scaffold 500).

In some embodiments, the expandable scaffold 500 is configured to bedeployed in multiple steps in order to provide a progressive, ormodular, treatment. For example, the reperfusion portion 502 havingsmall cell sizes advantageously can comprise at least a distal end ofthe expandable scaffold 500 such that only the reperfusion portion 502is deployed initially, thereby providing effective reperfusion of theoccluded vessel and facilitating natural lysis of a clot. After a periodof time (e.g., matter of minutes), the expandable scaffold 500 can befully deployed such that the removal portion 504 having larger cellsizes (e.g., an open cell structure configured to engage and grab orcapture the clot), which comprises a main central portion of theexpandable scaffold 500 in the illustrated embodiment, can be used toeffect removal of the clot. In some embodiments, the reperfusion portion502 comprises the proximal and/or distal end portion(s) of theexpandable scaffold 500.

IV. Expandable Tip Assemblies

As briefly described above, the expandable tip assemblies can include aproximal elongate member and a distal expandable scaffold. The elongatemember can comprise the majority of the expandable tip assembly with theexpandable scaffold comprising the expandable tip portion at a distalend of the expandable tip assembly. The expandable scaffold can becoupled to a distal end of the elongate member by any suitablemechanical attachment methods or devices (including, but not limited to,welding, soldering, adhesive, press-fitting, sheathing, molding, heatshrink tubing, curing, and/or combinations of the same). In someembodiments, the expandable scaffold is permanently coupled (e.g.,directly or indirectly) to the elongate member (e.g., is designed orconfigured not to be uncoupled from the elongate member or is integralwith the elongate member). The expandable scaffold can include a collar(e.g., a radiopaque marker) at its proximal end to facilitate coupling(e.g., welding, soldering, press-fitting) to the elongate member.

According to some embodiments, the expandable scaffold may optionally bedetachable from the elongate member if it is determined that theexpandable scaffold should remain in the patient. Detachment methodscomprise mechanical, electrical, hydraulic, chemical, thermal, and/orelectrolytic methods.

As described above, progressive, or modular, stroke therapy can befacilitated by the use of multiple expandable tip assemblies that aredesigned to perform different clot treatment functions (e.g.,reperfusion, maceration, removal). The expandable tip assemblies caninclude reperfusion (e.g., revascularization or recanalization) devicesthat provide therapeutically effective reperfusion and maceration ofemboli and embolus removal or capture devices that facilitate thecapture and extraction of emboli.

A. Elongate Member

FIGS. 6A-6C illustrate a side view, a top view, and exploded view of anembodiment of an expandable tip assembly 600. The expandable tipassembly includes an elongate member 605 and an expandable scaffold 610.In some embodiments, the elongate member 605 comprises a pusher tubehaving a lumen. In some embodiments, the lumen is sized and shaped toreceive a guidewire and/or allow for infusion of agents, fluids,compounds, or other materials to an occlusion site or target treatmentsite.

With reference to FIG. 6A, the elongate member 605 can comprise ahypotube. In some embodiments, the hypotube comprises a variable pitchand/or variable stiffness hypotube, which will be described in moredetail below in connection with FIGS. 7A and 7B. In some embodiments,the elongate member 605 comprises an intermittently cut hypotube. Forexample, the elongate member 605 can be intermittently cut by a laser toform a laser spiral-cut hypotube.

In some embodiments, the elongate member 605 comprises an outer diameterthat is less than the inner diameter of the microcatheter within whichit is to be inserted. In some embodiments, an outer diameter of theelongate member 605 can be between 0.005 inches and 0.030 inches,between 0.010 inches and 0.020 inches (e.g., 0.010 inches, 0.011 inches,0.012 inches, 0.013 inches, 0.014 inches, 0.015 inches, 0.016 inches,0.017 inches, 0.018 inches, 0.019 inches, 0.020 inches), between 0.015inches and 0.025 inches (e.g., 0.021 inches, 0.022 inches), oroverlapping ranges thereof. In some embodiments wherein the elongatemember 605 comprises a lumen, the inner diameter of the elongate member605 can be sufficiently large so as to allow infusion through theelongate member 605 to provide thrombolytic therapy with or without aguidewire being inserted therein. For example, the inner diameter of theelongate member 605 can be between 0.005 and 0.025 inches, between 0.005inches and 0.015 inches, between 0.010 inches and 0.015 inches, between0.015 and 0.020 inches (e.g., 0.163 inches), or overlapping rangesthereof. In some embodiments, the elongate member 605 extends beyond aproximal end of the expandable scaffold. The elongate member 605 caninclude a plurality of apertures allowing infusible lytic agents orother materials to be delivered to a subject embolus or to a treatmentlocation.

In some embodiments, the elongate member 605 is a guidewire (e.g.,delivery wire) without a lumen, thereby enabling the elongate member 605to have a smaller diameter to access smaller vessels. Infusion fluids orother materials can be delivered along the outsides of the elongatemember through the microcatheter.

The elongate member 605 can comprise stainless steel, titanium, one ormore polymers, polyimide, fluoropolymers, nitinol or other shape memoryalloys, vectran, kevlar, or other biocompatible materials. In oneembodiment, a stainless steel elongate member comprises spring temperedstainless steel. In some embodiments, the elongate member comprises acoil (e.g., a stainless steel coil). In some embodiments, the elongatemember 605 includes a spring element to facilitate clot removal.

With continued reference to FIG. 6A, the expandable tip assembly 600 caninclude radiopaque markers as described in more detail herein. Theradiopaque markers can include one or more distal markers 616 and one ormore proximal markers 618. The proximal radiopaque marker 918 cancomprise platinum and/or iridium; however, other radiopaque materialscan be used such as, but not limited to, gold, tantalum, palladium,tungsten, silver, lead, and/or radiopaque polymers, or combinationsthereof.

In some embodiments (for example, where the elongate member 605comprises stainless steel and the expandable scaffold 610 comprisesnitinol) it may not be possible to solder or otherwise couple theelongate member 605 to the expandable scaffold 610 due to their materialproperties. Accordingly, an element having a different material (e.g.,the radiopaque marker 618, which may comprise platinum) can bepositioned at the junction between the proximal end of the expandablescaffold 610 and the distal end of the elongate member 605 to facilitatethe coupling of the expandable scaffold 610 to the elongate member 605.

With reference to FIG. 6B, in some embodiments, a sleeve 611 covers thejunction between the distal end of the elongate member 605 and theproximal end of the expandable scaffold 610 and serves as a strainrelief for the junction. The sleeve 611 can comprise a heat-shrink tubeor clamp formed of polyethylene terephthalate (PET) or other heat-shrinktubing material, such as Pebax, nylon, polytetrafluoroethylene (PTFE),polyurethane, polyester, or other polymeric or elastomeric material. Insome embodiments, the sleeve 611 is positioned such that the distal endof the sleeve 611 stops at the expansion transition of the expandablescaffold 610. The length of the sleeve 611 can be between 10 cm and 20cm, between 15 cm and 25 cm, between 20 cm and 30 cm, between 30 cm and40 cm, between 35 cm and 45 cm (e.g., 40 cm), or overlapping rangesthereof. In embodiments wherein the elongate member 605 comprises alaser-cut hypotube, the sleeve 611 can have a length to cover thelaser-cut portion of the elongate member 605 (as shown in FIG. 6B). Theexpandable scaffold 610 can be attached or coupled to the elongatemember 605 by any suitable attachment method or device, such as, forexample, heat shrink tubing, adhesive, wound wire, suture, epoxy,interference fits, other low-profile mechanical attachment methodsand/or the like. In some embodiments, the tensile strength of thecoupling between the expandable scaffold 610 and the elongate member 605is between 0.5 lbs to 2 lbs (e.g., 0.75 lbs., 0.85 lbs., 1 lb., 1.25lbs, 1.5 lbs), which is well above the tensile strength required formanipulation within the cerebral vasculature.

FIG. 6D illustrates a side view of a portion of an embodiment of anexpandable tip assembly 600′. With reference to FIG. 6D, a polymericliner or jacket 613 can be incorporated within the elongate member 605′to improve trackability of a guidewire 620. In some embodiments, thepolymeric liner 613 extends beyond the distal tip of the elongate member605′ for guiding the guidewire 620 and preventing entanglement in theexpandable scaffold 610′. In one embodiment, the polymeric liner 613extends beyond the distal tip of the elongate member 605′ to a lengthgreater than the length of the expandable scaffold 610′ to direct theguidewire 620 and prevent it from entanglement in the expandablescaffold 610′.

FIGS. 7A and 7B illustrate a side view and a front view of an embodimentof an elongate member 705 comprising a variable pitch, laser spiral-cuthypotube. The elongate member 705 may be of variable stiffness that isable to track to and through the tortuous anatomy of the cerebralvasculature (e.g., internal carotid arteries, middle cerebral arteries,anterior cerebral arteries, vertebral arteries, basilar artery). Theelongate member 705 may be one or two pieces and may have greaterproximal pushability (stiffness) and greater distal flexibility(softness) to allow tracking to distal cerebral arteries.

For example, a distal portion (e.g., at least approximately the distal35 cm) of the variable stiffness hypotube can be more flexible to allowfor access through the tortuous vessels of the cerebral vasculature(e.g., to get above the carotid siphon (as shown in FIG. 35) and/or pastthe C1/C2 vertebral arteries). The elongate member 505 can graduallydecrease in stiffness from the proximal end to the distal end or candecrease in step-wise fashion. With reference to FIG. 7A, region Lillustrates a laser cut transition region of the variable-pitchhypotube. Regions P1, P2 and P3 comprise three regions of thevariable-pitch hypotube having variable pitch. In one embodiment, thepitch decreases from region P1 to region P2 and from region P2 to regionP3.

In some embodiments, a distalmost portion 714 of the elongate member 705comprises a ribbon coil portion. In other embodiments, the laser cuttransition region L can extend all the way to the distal end of theelongate member 705. FIGS. 7A and 7B also illustrate a polymeric liner713 extending outward from the distal end of the elongate member 705, asdescribed above in connection with FIG. 6D.

FIG. 7C illustrates embodiments of a distal end of a hypotube assembly750 that includes a solder joint 751 between a hypotube 752 and a ribboncoil 753 and a PET heat shrink 754. FIG. 7C illustrates example outerdiameter and length dimensions of the hypotube or delivery systemassembly.

FIG. 7D illustrates an embodiment of a distal end of a delivery systemassembly 760. In one embodiment, the delivery system assembly 760includes a proximal hypotube 762, a distal braid 763 and a polyimideliner 765. In one embodiment, the polyimide liner 765 may be a braid. Inone embodiment, the polyimide liner 765 improves trackability of theelongate member 705 over a guidewire.

B. Expandable Scaffold

FIGS. 8A-8C, 9A-9C, 10A-10F, 11A-11C, 12A-12D, 13A, 13B, 14, 15A-15C,16, 17A-17E, 18A-18F, 19, 20, 21A and 21B generally illustrate variousembodiments of expandable scaffolds. The features, designs, and/orelements described in connection with particular embodiments ofexpandable scaffolds herein can be used in any of the other embodimentsof expandable scaffolds described herein.

FIGS. 8A-8C illustrate a perspective view, a side view, and a top viewof an embodiment of an expandable scaffold 810. In accordance with someembodiments, the expandable scaffold 810 comprises a self-expandingscaffold without the need for mechanical actuation; however, theexpandable scaffold 810 can be mechanically expanded or inflated inother embodiments. For example, the expandable scaffold 810 can compriseshape memory material, such as a nickel titanium alloy. In oneembodiment, the expandable scaffold 810 comprises a nitinol device ormember. In some embodiments, the expandable scaffold 810 comprises aclosed cell design (for example, as shown in FIGS. 8A-8C); however, inother embodiments, an expandable scaffold can comprise an open celldesign. The closed cell design advantageously can facilitaterecapturability and resheathability of the expandable scaffold 810. Theexpandable scaffold 810 can be configured to transition between acompressed, or non-expanded, configuration or state and a deployed, orexpanded, configuration or state.

The expandable scaffold 810 can comprise a stent-like member comprisedof a pattern of struts 812 and cells 814. In one embodiment, theexpandable scaffold 810 comprises a self-expanding microstent. Thestruts 812 can permit flexion and extension of the expandable scaffold810 to navigate through curved vessels. The expandable scaffold 810 canbe formed by laser cutting a tube. For example, the expandable scaffold810 can comprise a nitinol laser-cut tube. The cut tube scaffoldadvantageously facilitates inclusion of a tapered proximal end. In someembodiments, an expandable scaffold can comprise a rolled woven mesh orbraided scaffold. A rolled mesh scaffold advantageously can improvevessel apposition and adjust to varying vessel diameters; however, therolled mesh scaffold may be configured so as to not collapse under aload but to curl up instead, thereby making it difficult to resheath therolled mesh scaffold in situ. In some embodiments, the expandablescaffold 810 does not comprise a rolled mesh scaffold. In someembodiments, the expandable scaffold 810 does not have a backboneextending along its length, which may be configured to distribute a loadalong the entire length or a portion of the scaffold.

In some embodiments, the expandable scaffold 810 (e.g., for intracranialuse) can be flexible, precisely delivered, retrievable, able to berepositioned, atraumatic, available in various lengths and diameters,thin-walled and radiopaque. The expandable scaffold 810 can be deliveredthrough a microcatheter, allowing standard microcatheter/wire techniquesto reach locations inaccessible to standard over-the-wire stents. Inaccordance with some embodiments, the expandable scaffold 810advantageously can be retrieved and repositioned after completedelivery, if its position is felt to be suboptimal. In some embodiments,the expandable scaffold 810 conforms completely to the normal vesselgeometry and is not prone to strut opening on convexities. In someembodiments, the expandable scaffold 810 is adapted so as to provide acontinuous radial pressure when in the expanded state. In someembodiments, the expandable scaffold 810 is MR compatible.

With reference to FIG. 8B, the expandable scaffold 810 includes one ormore laser-cut apertures or eyelets 808 that can receive radiopaquemarkers. The radiopaque markers can comprise pegs that can be press-fitand/or adhered within the laser-cut apertures 808. With reference toFIG. 8C, the expandable scaffold 810 can include tether lines or tangs819 that are arranged in an equally spaced or substantially equallyspaced fashion around the entire circumference of a proximal collar 809of the expandable scaffold. The tether lines or tangs 819 can extendconcentrically from the proximal collar 809. Although not illustrated inall of the figures, each of the embodiments of the expandable scaffoldsdescribed herein can include one or more radiopaque markers.

FIGS. 9A-9C illustrate side, top, and front views of an expandablescaffold 910. With reference to FIGS. 9A-9C, the expandable scaffold 910can include tether lines or tangs 919 that extend eccentrically, oroff-center, from a collar of 909 the expandable scaffold 910. Forexample, as best shown in FIGS. 9A and 9C, the tether lines 919 canextend only from one side (e.g., from one half, below center, abovecenter) of the proximal end of the expandable scaffold 910. Theeccentricity advantageously can improve blood flow by reducing theprofile or amount of space of the vessel occupied by the proximal end ofthe expandable scaffold 910.

As best shown in FIGS. 9A and 9C, the expandable scaffold 910 mayprovide an everted or scooped out geometry (e.g., an everted or open,tapered or angled section) to facilitate recapture of the expandablescaffold 910 into the microcatheter. For example, the everted,scalloped, scooped-out or cut-out geometry can comprise an open mouth orport 907 at a proximal end of the expandable scaffold 910 to facilitateresheathing. The open mouth or port 907 can also enhance blood flowthrough the expandable scaffold 910. In some embodiments, an everted oropen tapered or angled section, such as an open mouth or port, canfacilitate clot capture and extraction (e.g., can allow passage of aclot from the exterior of the scaffold 910 to the interior of thescaffold 910). Using everted scaffolds, emboli can be removed withoutcompromising access, as the emboli become enmeshed with the scaffoldsand can be removed without vessel damage. For example, a clot can enterthe scaffold 910 via the mouth or port 907. In some embodiments, aportion of the clot can be caught or captured within the mouth or port907 and a portion of the clot can be caught or captured on an externalsurface of the scaffold 910. The everted section (e.g., mouth or port907) can be located at a distal or proximal end of the scaffold 910 oranywhere along the length of the scaffold 910. In some embodiments, themouth or port 907 can be positioned to surround a clot and capture theclot within the scaffold 910.

With reference to FIGS. 9B and 9C, the expandable scaffold 910 cancomprise radiopacity for imaging purposes. The expandable scaffold 910can include one or more radiopaque markers 916 at a distal end of thescaffold 910. The radiopaque markers 916 at the distal end of thescaffold 910 can be pressed into pre-laser cut apertures or eyeletsdesigned to receive them. In some embodiments, the radiopaque markers916 comprise platinum or gold; however, other radiopaque materials canbe used such as, but not limited to, tantalum, palladium, tungsten,silver, lead, and/or radiopaque polymers, or combinations thereof. Thedistal radiopaque markers 916 can be ground flush to provide a smooth,low profile (as best shown in FIG. 9C). The expandable scaffold 910 caninclude a radiopaque marker 918 at a proximal end of the scaffold 910.As described above, one or more proximal radiopaque markers can bepositioned at the junction between an expandable scaffold and the distalend of an elongate member to facilitate tracking and to facilitatecoupling of the expandable scaffold to the elongate member.

The design of the expandable scaffold 910, according to severalembodiments, includes a pattern whereby when the expandable scaffold 910is retracted, it is able to fully retract into the microcatheter. Theexpandable scaffold 910 advantageously can comprise features thatfacilitate single-step resheathing within the microcatheter. Withreference to FIGS. 9A-9C, the expandable scaffold 910 can comprise atapered proximal end having a plurality of tether lines or tangs 919. Insome embodiments, the tether lines 919 can be relatively long tofacilitate retraction. An expandable scaffold comprising a laser cuttube can provide enhanced resheathing ability over a rolled mesh or ascaffold having a backbone along its length. In some embodiments, thetether lines 919 comprise between one-tenth and one-third (e.g., aboutone-tenth, about one-ninth, about one-eighth, about one-seventh, aboutone-sixth, about one-fifth, about one-fourth, about one-third) of thetotal length of the expandable scaffold 910.

In some embodiments, the expandable scaffolds can be open at theirdistal, or downstream, end because distal embolization is not a concernwhen blood flow is first restored. Although the embodiments of thescaffolds described above have open distal ends, in some embodiments, acapturing device (e.g., scaffold) may include a distal portion that isresistant to the passage of a clot or large portion of a clot from theinterior of the capturing device to the exterior of the capturingdevice. FIGS. 12A-12D, 15A-15C, 17A, 17B, 18A-18F, 19, and 20 illustrateexpandable scaffolds with closed or substantially closed distal ends. Aclosed distal end may prohibit the escape of a clot out of the distalend while the capturing device is retracted. For example, the distal endof the capturing device may be closed, such that the open-cell structureat the distal end is more confined than the open-cell structure at themiddle section of the capturing device or other section configured toaccept a clot.

FIGS. 10A-10C illustrate a perspective view, a side view and a frontview of an expandable scaffold 1010 in a compressed configuration andFIGS. 10D-10F illustrate a perspective view, a side view and a back viewof the expandable scaffold 1010 in an expanded configuration. Theexpandable scaffold 1010 comprises a laser-cut tube. The cut patternincludes five straight or substantially straight cuts equally spacedaround the circumference of the expandable scaffold 1010. The struts1012 formed by the laser cuts are not interconnected. The expandablescaffold 1010 has a tapered proximal end 1022 and is substantiallyclosed at its proximal end 1022 and distal end 1024. The relativelylarge open spaces between the struts 1012 can provide sufficient bloodflow through the expandable scaffold 1010. The maximum diameter of theexpandable scaffold 1010 in the expanded configuration is located nearthe distal end 1024. The expandable scaffold 1010 has a variablediameter along its length.

FIG. 11A illustrates a side view of an embodiment of an expandablescaffold 1110 in a compressed configuration and FIGS. 11B and 11Cillustrate a perspective view and a side view of the expandable scaffoldof FIG. 11A in an expanded configuration. The expandable scaffold 1110comprises a laser-cut tube having a cut pattern that includes fourstraight or substantially straight cuts equally spaced around thecircumference of the expandable scaffold 1110. The struts 1112 formed bythe laser cuts are not interconnected. The expandable scaffold 1110 hasa closed proximal end 1122 and a closed distal end 1124. The proximalend 1122 and the distal end 1124 are substantially evenly tapered in theexpanded configuration, with the maximum diameter occurring in themiddle of the expandable scaffold 1110.

FIG. 12A illustrates a cut file of an embodiment of an expandablescaffold 1210 formed of a laser-cut tube. FIGS. 12B and 12C illustrate aperspective view and a side view of the expandable scaffold formed fromthe cut profile of FIG. 12A in its expanded configuration. As best shownin FIG. 12C, the expandable scaffold 1210 can include an open-celledconfiguration. FIG. 12C illustrates that the expandable scaffold hasopen gaps 1217 between segments of the expandable scaffold 1210. FIG.12D illustrates a two-dimensional view of the cut profile of FIG. 12A inits expanded configuration. The expandable scaffold 1210 includesrelatively long tether lines or tangs 1219 at a proximal end 1222 of thescaffold 1210. The expandable scaffold 1210 is tapered at its proximalend 122 and its distal end 1224. The expandable scaffold 1210 includes aseries of interconnected struts and bridges.

FIGS. 13A and 13B illustrate cut profiles of an embodiment of anexpandable scaffold 1310 in its compressed and expanded configurations,respectively. The expandable scaffold 1310 includes an open-cell design.As shown in FIG. 13B, the expandable scaffold 1310 has an open distalend 1324 and a plurality of tether lines or tangs 1319 at itssubstantially closed proximal end 1322. The expandable scaffold 1210comprises a pattern of interconnected struts arranged in a zig-zag-likemanner to form substantially Z-shaped cells 1323.

FIG. 14 illustrates a laser cut profile of the expandable scaffold 810of FIGS. 8A-8C and FIG. 16 illustrates a laser cut profile of theexpandable scaffold 910 of FIGS. 9A-9C.

FIG. 15A illustrates a laser cut profile of an embodiment of anexpandable scaffold 1510 and FIGS. 15B and 15C illustrate a perspectiveview and a side view of the expandable scaffold 1510 formed from the cutprofile of FIG. 15A in its expanded configuration. The expandablescaffold 1510 comprises an open-cell device that is substantially closedat its proximal end 1522 and its distal end 1524. The expandablescaffold 1510 includes a similar cell pattern as the expandable scaffold1210 of FIGS. 12A-12D; however, the expandable scaffold 1510 includesfewer tether lines or tangs 1519.

FIG. 17A illustrates a laser cut profile of an embodiment of an offsetexpandable scaffold 1710 and FIGS. 17B-17E illustrate a side view, afront view, a back view, and a section view of the offset expandablescaffold 1710 formed from the laser cut profile of FIG. 17A. The tetherlines or tangs 1719 extend from a proximal collar 1709 that is offset,or eccentric, from a central longitudinal axis of the expandablescaffold 1710. The offset, or eccentric, deployment can facilitateincreased blood flow through the expandable scaffold 1710 because theproximal end 1722 occupies less area of the vessel. In accordance withsome embodiments, the offset expandable scaffold 1710 comprises anoffset clot basket configured to provide effective clot removal. In someembodiments, the offset expandable scaffold 1710 includes struts ortangs at a proximal end 1722 that have a larger width or thickness thanthe struts along a main body portion of a distal end 1724 of theexpandable scaffold 1710.

FIGS. 18A-18C illustrate a perspective view, a side view, and a frontview of an embodiment of a spiral expandable scaffold 1810 in itscompressed configuration and FIGS. 18D-18F illustrate a perspectiveview, a side view, and a front view of the spiral expandable scaffold1810 in its expanded configuration. With reference to FIGS. 18A and 18B,the spiral expandable scaffold 1810 is formed of a laser cut tubewherein the laser cuts are straight or substantially straight from aproximal end 1822 of the expandable scaffold 1810 toward the distal end1824 (e.g., more than half of the total length) and then veer off at anangle at the distal end 1824, thereby forming a spiral expandablescaffold when expanded. The spiral expandable scaffold 1810advantageously can be used to facilitate effective clot removal.

FIG. 19 illustrates a perspective view of an embodiment of an expandablescaffold 1910. In some embodiments, the expandable scaffold 1910comprises a woven basket. The expandable scaffold 1910 is substantiallyclosed or closed at its proximal end 1822 and its distal end 1924. Theexpandable scaffold includes 1910 longitudinal or horizontal struts 1913extending from a proximal collar 1914 to a distal collar 1918 that areequally angularly spaced and a plurality of vertical struts 1919interconnecting the longitudinal or horizontal struts 1913. In someembodiments, the horizontal struts 1913 have greater thickness or widththan the vertical struts 1919.

FIG. 20 illustrates a perspective view of an embodiment of a wovenexpandable scaffold 2010 configured for clot retrieval or extraction. Insome embodiments, the woven expandable scaffold 2010 has wires ofincreased thickness adjacent to its proximal end 2022 to provide tensilestrength for opening the expandable scaffold 2010. The expandablescaffold 2010 can comprise a mesh or woven basket having low porosityfine wires in the basket area 2021 to support a clot and thicker wiresor tether lines 2023 at the proximal end 2022 that open the expandablescaffold 2010 and give strength to the woven expandable scaffold 2010.

The resheathing features of the expandable scaffolds described above(e.g., tapered proximal end, long tether lines, everted sections,eccentricity) advantageously can provide pain reduction and reduced lossof endothelial cells during treatment. The resheathing features can alsofacilitate clot capture and extraction. For example, expandablescaffolds having tapered proximal ends (e.g., expandable scaffold 610,expandable scaffold 910) taper away from a vessel wall as the expandablescaffold is withdrawn, thereby reducing vessel scraping and risk ofvessel perforation or vasospasm. The reduced vessel scraping can reducepain experienced by a patient and reduce loss of endothelial cellsduring treatment. The non-tapered distal end can remain fully deployedand in contact with a vessel wall during resheathing.

The expandable scaffolds (for example, but not limited to, expandablescaffold 610, expandable scaffold 810, expandable scaffold 910) may becoated with, covered by, or otherwise include substances impartinglubricous characteristics and/or therapeutic substances, as desired.According to several embodiments, coatings include vasodilators such aspapaverine and nimodipine, rapamune (e.g., Sirolimus), paclitaxel,anti-coagulant materials, anti-platelet materials, or combinationsthereof. Additionally, at least heparin and other coating materials ofpharmaceutical nature may be used. In some embodiments, the expandablescaffolds can comprise a coating that increases or enhances clotadhesion to an expandable scaffold, such as a thrombogenic material thatpromotes the formation of fibrin bonds with the expandable scaffold or amaterial that enhances platelet activation or growth. In someembodiments, the expandable scaffolds are configured to benon-thrombogenic and, in some embodiments, can further be used withoutplacing subjects on an anti-clotting drug (including but not limited toacetylsalicylic acid (e.g., aspirin) and clopidogrel (e.g., Plavix®)).

The length of the expandable scaffolds described herein can vary. Insome embodiments, the length of the expandable scaffolds is between 10mm and 50 mm, between 20 mm and 40 mm, between 25 mm and 35 mm (e.g., 30mm), less than 10 mm, greater than 50 mm, or overlapping ranges thereof.The diameter of the expandable scaffolds varies between the compressedand expanded configurations. The expanded diameter of the expandablescaffolds can be between 1 mm and 10 mm, between 1.5 mm and 6 mm,between 2 mm and 5 mm. In some embodiments, the expanded diameter is 1mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In someembodiments, the expanded diameter can be greater than 10 mm.

The expandable scaffolds can be sized and configured to be deployed inparticular blood vessels. For example, expandable scaffolds designed tobe deployed within a middle cerebral artery can have an expandeddiameter of between 1.5 mm and 3 mm and length between 10 mm and 30 mm.Expandable scaffolds designed to be deployed in an internal carotidartery can have an expanded diameter of between 3 mm and 6 mm and alength between 10 mm and 50 mm. In some embodiments, expandablescaffolds designed to be deployed in a posterior cerebral artery canhave an expanded diameter of between about 2 mm and 3 mm and a lengthbetween 10 mm and 30 mm. Expandable scaffolds designed to be deployed ina basilar artery can have an expanded diameter between 3 mm and 4 mm anda length between 10 mm and 40 mm and expandable scaffolds designed to bedeployed in a vertebral artery can have an expanded diameter between 3mm and 4 mm and a length between 10 mm and 60 mm. Expandable scaffoldshaving an expanded diameter of 5 mm can be used as a default in anycerebral artery but may experience significant cell deformation invessels having a diameter less than 5 mm.

1. Expandable Scaffold Parameters or Characteristics

Turning to FIGS. 21A and 21B, according to several embodiments,characteristics of an expandable scaffold 2110 may be controlled tomodify the effect of the expandable scaffold 2110 to achieve one or moreof maceration, removal, and lysis of a clot. For example, hoop strength,stiffness, cell size, strut length, strut width, and strut thickness ofthe expandable scaffold 2110 may be varied to provide customizabletherapies to a clot. In accordance with some embodiments, the expandablescaffold exhibits sufficient radial force to expand to a vessel wall buthas a large enough cell size to increase the efficacy of removal (e.g.,a cell size is configured to facilitate both reperfusion of the bloodvessel and capture of the clot).

Blood vessels may experience loads from a variety of sources, such asthe expansion of the expandable scaffold 2110. Pressures applied to anycylindrical structure, such as a blood vessel, result in hoop, orcircumferential loading of the vessel (FIG. 21A). Both the appliedpressure and the resulting hoop stress have units of force per unitarea, but these may differ in direction. As used herein, “pressure”refers to the force normal to the vessel wall, divided by the surfacearea of the lumen. As used herein, “hoop stress” is the circumferentialload in the vessel wall divided by the cross-sectional area of thevessel wall (length times wall thickness).

The relationship between the pressure (p) and the hoop stress (σ) in athin-walled cylindrical object, such as the expandable scaffold 2110,may be expressed as:

$\begin{matrix}{{\sigma = \frac{\rho\varphi}{2t}},} & \left( {{Eq}.\mspace{14mu} 1} \right)\end{matrix}$

where “φ” is the diameter of the expandable scaffold 2110 and “t” is thewall thickness of the expandable scaffold 2110. The hoop force (F_(θ))in a vessel wall may be expressed as:

$\begin{matrix}{{F_{\theta} = {{\sigma \; {tL}} = \frac{{\rho\varphi}\; L}{2}}},} & \left( {{Eq}.\mspace{14mu} 2} \right)\end{matrix}$

where “L” is the length of the expandable scaffold 2110 (or length“L_(s)” of a strut, depending on the scope of analysis). The hoop forceper unit length (f_(θ)) may be expressed as:

$\begin{matrix}{f_{\theta} = {\frac{F_{\theta}}{L} = {{\sigma \; t} = {\frac{\rho\varphi}{2}.}}}} & \left( {{Eq}.\mspace{14mu} 3} \right)\end{matrix}$

a. Hoop Stiffness

“Stiffness,” or the elastic response of a device to an applied load,reflects the effectiveness of the expandable scaffold 2110 in resistingdeflection due to vessel recoil and other mechanical events. “Stiffness”is the inverse of “compliance,” or diameter change (ΔΦ) at a specificapplied pressure (p). As shown in FIG. 21A, the expandable scaffold 2110shown in cross section may experience a change in diameter (ΔΦ) as itexpands from a compressed state 2101 to an uncompressed state 2102. Thehoop stiffness (k_(θ)) of the expandable scaffold 2110 may be expressedas the hoop force per unit length (f_(θ)) required to elastically changeits diameter (ΔΦ), or:

$\begin{matrix}{k_{\theta} = {\frac{f_{\theta}}{\Delta\varphi}.}} & \left( {{Eq}.\mspace{14mu} 4} \right)\end{matrix}$

A change in diameter (ΔΦ) of expandable scaffold 2110 due to an appliedload is related to the geometry of expandable scaffold 2110 as expressedby:

$\begin{matrix}{{{\Delta\varphi} \propto \frac{f\; \varphi \; {nL}_{s}^{3}}{{Ew}^{3}t}},} & \left( {{Eq}.\mspace{14mu} 5} \right)\end{matrix}$

where “L_(s)” is the length of a strut (as shown in FIG. 22), “w” is thestrut width (as shown in FIG. 11), “t” is the thickness of expandablescaffold (as shown in FIG. 22), “n” is the number of struts around thecircumference of expandable scaffold 2110, and “E” is the elasticmodulus of the material. Combining Eq. 3 with Eq. 5, the change indiameter (ΔΦ) of expandable scaffold 2110 may be related to an appliedpressure load (p) by:

$\begin{matrix}{{{\Delta\varphi} \propto \frac{{\rho\varphi}\; {nL}_{s}^{3}}{{Ew}^{3}t}},} & \left( {{Eq}.\mspace{14mu} 6} \right)\end{matrix}$

Combining Eq. 4 and Eq. 6, the hoop stiffness (k_(θ)) may be expressedas:

$\begin{matrix}{k_{\theta} \propto {\frac{{Ew}^{3}t}{{nL}_{s}^{3}}.}} & \left( {{Eq}.\mspace{14mu} 7} \right)\end{matrix}$

Thus, hoop stiffness (k_(θ)) has a cubic relationship with strut width(w), a linear relationship with strut thickness (t), an inversely linearrelationship with number of struts about the circumference (n), and aninversely cubic relationship with the strut length (L_(s)).

In contrast to symmetrical radial expansion and compression, an unevenload (i.e., pinching load) may be applied to an external surface of aportion of the expandable scaffold 2110, resulting in radiallyasymmetric deflection (Δz). For example, as shown in FIG. 21B, theexpandable scaffold 2110 may be squeezed between two opposite loads,whereby the expandable scaffold 2110 is subjected to a pinching load.Under a pinching load, the expandable scaffold 2110 may deflect from aninitial state 2103 to a deflected state 2104. A pinching load may causestruts 2220 (see FIG. 22) to be bent in a manner other than about thecircumference. Pinching stiffness (k_(p)), or the force required tocause radially asymmetric deflection (Δz) may be generalized by theexpression:

$\begin{matrix}{k_{p} \propto {\frac{{Et}^{3}w}{{nL}_{s}^{3}}.}} & \left( {{Eq}.\mspace{14mu} 8} \right)\end{matrix}$

Under a pinching load, the pinching stiffness (k_(p)) of the expandablescaffold 2110 has a cubic relationship with strut thickness (t) and alinear relationship with strut width (w). This is relationship is theinverse of the strut's influence on hoop stiffness (k_(θ)). Thus, strutthickness (t) has a dominant role in pinching stiffness (k_(p)) andstrut width (w) has a dominant role in hoop stiffness (k_(θ)).

According to several embodiments, a clot in an otherwise substantiallyradially symmetric vessel may tend to cause radially asymmetricdeflection of the expandable scaffold 2110 as it is expanded against theclot. Both hoop stiffness (k_(θ)) and pinching stiffness (k_(p)) of theexpandable scaffold 2110 play a role in how the expandable scaffold 2110interacts with the clot.

b. Lengths and Expansion Diameters

The sizes of the expandable scaffolds can vary depending on the size ofthe particular vessel in which they are configured to be inserted. Forexample, the lengths of the expandable scaffolds can vary from 1 cm to 5cm (e.g., from 1 cm to 4 cm, from 2 cm to 5 cm, from 2 cm to 4 cm,overlapping ranges thereof, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4cm, 4.5 cm, 5 cm) and the expansion diameter can vary from 1 mm to 6 mm(e.g., from 1 mm to 4 mm, from 2 mm to 6 mm, from 3 mm to 5 mm,overlapping ranges thereof, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm)depending on the vessel to be addressed by the particular expandable tipassembly. In some embodiments, the expandable scaffolds can beconfigured to expand to diameters larger than 5 mm (e.g., 6 mm, 7 mm, 8mm, 9 mm, 10 mm) or less than 2 mm (e.g., 1.8 mm, 1.6 mm, 1.4 mm, 1.2mm, 1.0 mm).

In some embodiments, an expandable tip assembly can be selected based onexpansion diameter of the expandable scaffold. An expandable tipassembly having an expandable scaffold that has a maximum expansiondiameter roughly equivalent to the vessel diameter can be used to reducecell deformation and minimize risk of vessel damage. If the expandabletip assembly is to be used for clot removal or extraction, selecting anexpandable tip assembly having an expandable scaffold that has a maximumexpansion diameter roughly equivalent to the vessel diameter can preventthe clot from sliding by the expandable scaffold, thereby increasing theefficacy of clot removal in several embodiments. For example, someexpandable scaffolds can have an expansion diameter configured to beused in 3 mm vessels and other expandable scaffolds can have anexpansion diameter configured to be used in 5 mm vessels. In someembodiments, an expandable tip assembly having an expandable scaffoldthat has a maximum expansion diameter greater than the vessel diameteror less than the vessel diameter is selected as desired and/or requiredby particular circumstances.

c. Radial Force (Chronic Outward Force and Radial Resistive Force)

According to several embodiments, the expandable scaffold 2110 mayprovide both a chronic outward force (“COF”) and a radial resistiveforce (“RRF”). As used herein, chronic outward force (“COF”) is thecontinuing radial opening force of a self-expanding scaffold acting on avessel wall after having reached equilibrium with the vessel wall. Asused herein, radial resistive force (“RRF”) is the force generated bythe self-expanding scaffold to resist compression, or the force requiredto compress the scaffold. Generally, RRF is expressed in relation to theamount of relative compression to be achieved. Generally, COF and RRFare expressed in terms of force per unit length (e.g., N/mm).

According to several embodiments, the expandable scaffold 2110 may havea range of COF per unit length across given diameters (e.g., 1 mm to 4.5mm). In some embodiment, the COF per unit length of the expandablescaffold 2110 across given diameters is substantially uniform, orconstant. In some embodiments, the COF per unit length of the expandablescaffold 2110 across given diameters (e.g., 1 mm to 4.5 mm) slightlydecreases with increasing vessel diameter. For example, the COF may befrom about 0.00590 N/mm to about 0.0090 N/mm at a diameter of about 2.0mm and a COF from about 0.00165 N/mm to about 0.0038 N/mm at a diameterof about 4.5 mm. In some embodiments, the COF per unit length of theexpandable scaffold 2110 decreases by less than 10% to 90% (e.g., lessthan 10%, less than 20%, less than 30%, less than 40%, less than 50%,less than 60%, less than 70%, less than 80%, less than 90%) over a rangeof expansion diameters from 1.5 mm to 4.5 mm. In one embodiment, the COFper unit length of the expandable scaffold 2110 decreases by between 50%to 75% over a range of expansion diameters from 1.5 mm to 4.5 mm. Insome embodiments, the COF per unit length of the expandable scaffold2110 across given diameters (e.g., 1 mm to 4.5 mm) is substantiallynon-zero across the entire range of diameters.

According to several embodiments, the expandable scaffold 2110 may havea range of RRF per unit length across given diameters (e.g., 1.5 mm to4.5 mm). For example, RRF may be from about 0.011 N/mm to about 0.016N/mm at a diameter of about 2.0 mm and from about 0.005 N/mm to about0.007 N/mm at a diameter of about 4.5 mm.

According to several embodiments, the expandable scaffold 2110 may havean average COF per unit across a diameter of 2.0 mm to 4.5 mm lengthacross a diameter of 2 mm to 4.5 mm of between about 0.0016 N/mm and atleast about 0.0090 N/mm, (e.g., between about 0.0020 N/mm and about0.0070 N/mm, between about 0.0025 N/mm and about 0.0065 N/mm, betweenabout 0.00165 N/mm and about 0.0090 N/mm, between about 0.0023 N/mm andabout 0.0073 N/mm, between about 0.0030 N/mm and about 0.0059 N/mm, oroverlapping ranges thereof). According to several embodiments, theexpandable scaffold 2110 may have an average RRF per unit length acrossa diameter of 2 mm to 4.5 mm of between about 0.0067 N/mm and about0.0138 N/mm (e.g., between about 0.0065 N/mm and about 0.0140 N/mm,between about 0.0070 N/mm and about 0.0130 N/mm, between about 0.0083N/mm and about 0.0127 N/mm, or overlapping ranges thereof). Therapyprovided within these ranges may provide effective maceration toward thelower end of the range and effective removal toward the upper end of therange.

According to several embodiments, an expandable scaffold havingrelatively low COF and RRF is effective for facilitating maceration of aclot. For example, an expandable scaffold having an average COF ofbetween about 0.015 N and about 0.0040 N (e.g., 0.12 N to 0.004 N)across a diameter of 1.5 mm to 4.5 mm and having an average RRF betweenabout 0.0050 N and about 0.0220 N (e.g., 0.0080 N to 0.0200 N) across adiameter of 1.5 mm to 4.5 mm can provide effective therapy requiringmaceration of a clot. According to several embodiments, an expandablescaffold having relatively high COF and RRF is effective forfacilitating removal of a clot. For example, an expandable scaffoldhaving an average COF of between about 0.0015 and about 0.0090 (e.g.,between about 0.0040 N and about 0.0090 N, between about 0.0015 N andabout 0.0060 N, between about 0.0020 N and about 0.0080 N, oroverlapping ranges thereof) and having an average RRF between about0.0060 N and about 0.0200 N (e.g., about 0.0060 N to about 0.0150 N,about 0.0070 N to about 0.0160 N, about 0.0100 to about 0.0200 N, oroverlapping ranges thereof) can provide effective therapy requiringremoval of a clot.

d. Cell Design

FIG. 23 illustrates a close-up schematic representation of a cell of anembodiment of an expandable scaffold 2310. According to severalembodiments, cell size contributes to the effect that the expandablescaffold has on a clot. As shown in FIG. 23, each open cell 2350 of theexpandable scaffold 2310 may have a cell height and cell length,providing exposure from an interior portion of the expandable scaffold2310 to an exterior portion of the expandable scaffold 2310. The cells2350 of the expandable scaffold 2310 may include struts 2360 and bridges2365 connecting struts 2360. Bridges 2365 may be of a variety of shapesand sizes, including “C” shapes, “S” shapes, straight shapes, etc. Cells2350 may form a variety of shapes, including diamonds, parallelograms,rectangles, and other polygonal shapes.

According to several embodiments, a variety of cell sizes and geometriesmay be provided to achieve desired outcomes during therapy. According toseveral embodiments, as shown in FIGS. 24A, 24B, 25A, 25B, 26A, 26B,27A, and 27B, a variety of cell sizes and geometries may be provided toachieve desired outcomes during therapy. FIGS. 24A and 24B show aNeuroForm³™ (by Boston Scientific® of Boston, Mass.) device. FIGS. 25Aand 25B show an Enterprise™ device (by Cordis® of Bridgewater, N.J.).FIGS. 26A and 26B show a Solitaire™ AB device (by ev3® of Plymouth,Minn.). FIGS. 27A and 27B show an IRIIS™ device (by MindFrame® ofIrvine, Calif.). The IRIIS™ device of FIGS. 27A and 27B is an embodimentof the expandable tip assemblies described herein.

As shown in FIGS. 28, 29A, 29B, and 29C, individual cells 210 are shownwith emphasis. FIG. 28 shows views of each of a Solitaire™ AB device, aNeuroForm³™ device, and an Enterprise™ device. FIGS. 29A, 29B, and 29Ceach show an embodiment of an expandable scaffold (e.g., a MindFrameIRIIS™ device). The respective cell sizes of each are shown withemphasis. In particular, FIGS. 29A, 29B, and 29C show similar cellgeometries with distinct cell sizes and the impact on the overallstructure of the respective device. A relatively larger cell size isshown in FIG. 29A, with a relatively smaller cell size shown in FIG. 29Cand an intermediate cell size shown in FIG. 29B.

According to several embodiments, an expandable scaffold (e.g., aremoval scaffold or combination reperfusion and removal scaffold) of anexpandable removal device) having a larger cell size facilitates removalof a clot by allowing larger portions of the clot to be isolated as theclosed portions (e.g., struts) of the cells apply pressure and force tothe clot. The larger cell sizes cause larger portions of the clot toremain within the scaffold, whereby the relatively larger portions maybe more readily captured and removed with the expandable scaffold orother devices. The relatively large cells allow for more of the clot toenter, protrude or penetrate into the interior of the expandablescaffold (e.g., from the side exterior of the expandable scaffold),thereby enhancing clot adhesion and increasing the likelihood of clotcapture. The relatively large cells can allow the expandable scaffold tomore fully expand to the vessel diameter, thereby providing a shearingeffect at the clot adhesion site to break sticky, firm bonds that mayhave formed between the clot and the vessel wall. The relatively largecells advantageously can allow for expansion to a greater diameter witha lower requisite radial force. Variation of radial strength can affectremoval characteristic such as the ability to navigate through theintracranial vessel tortuosity.

According to several embodiments, the expandable scaffold having a smallcell size facilitates lysis and maceration of a clot by breaking theclot into smaller portions. The smaller cell sizes cause smallerportions of the clot to remain, whereby more surface area of the clot isexposed to ambient materials for facilitating lysis. Variation of thecell size may affect clot lysis by varying the amount of surface areaapplying pressure from the structure to the clot. For example, smallercell sizes will generally provide a greater amount of structure totransfer pressure and forces to a clot. Furthermore, a structure havingsmaller cells may provide a more consistently shaped channel (with feweror less dramatic inflection points) for recanalization by more evenlydistributing the outward forces and pressures. The improvedrecanalization in turn facilitates improved lysis by virtue of betterexposure of the clot to vascular flow.

Referring back to FIGS. 27A and 27B, an embodiment of an expandablescaffold 2710 having a cell size and geometry that is configured forreperfusion and maceration is illustrated. According to severalembodiments, the expandable scaffold 2710 may have cells 2750 of celllength from at least about 0.100 inches to at least about 0.250 inches(e.g., about 0.100 inches to about 0.175 inches, about 0.100 inches toabout 0.150 inches, about 0.125 inches to about 0.185 inches, about0.150 inches to about 0.200 inches, about 0.200 inches to about 0.250inches, or overlapping ranges thereof). According to severalembodiments, the expandable scaffold 2710 may have cells 2750 of cellheight from about 0.035 inches to about 0.100 inches (e.g., about 0.035inches to about 0.075 inches, about 0.040 inches to about 0.055 inches,about 0.050 inches to about 0.065 inches, about 0.085 inches to about0.100 inches, or overlapping ranges thereof). For example, theexpandable scaffold 2710 having cells 2750 of cell length of about 0.120inches and cell height of about 0.050 inches may be effective formacerating a clot to which the expandable scaffold 2710 is applied. Byfurther example, an expandable scaffold having cells of cell length ofabout 0.250 inches and cell height of about 0.100 inches may beeffective for removing a clot to which the expandable scaffold isapplied.

According to several embodiments, the cell height and cell length ofeach cell may yield an area defined by the boundaries of the cell. Forexample, the expandable scaffold 1110 may have cells each having an areaof between about 0.006 square inches to about 0.025 square inches,between about 0.010 square inches to about 0.020 square inches, oroverlapping ranges thereof. More specifically, each cell may yield anarea defined by the boundaries of the cell. According to severalembodiments, an expandable scaffold having small cells and high radialstrength provides better channel development and maceration withrelatively softer clots. According to several embodiments, an expandablescaffold having larger cells and high radial strength will providebetter maceration and retrieval for firm, white clots.

In accordance with some embodiments, the cell size varies based on thesize of the vessel into which the expandable tip assembly is configuredto be inserted. In one embodiment, for an expandable tip assemblyconfigured to be inserted into vessels having a diameter of between 1.5mm and 4.5 mm and configured to facilitate reperfusion and maceration,the expandable scaffold can have a cell length of about 0.080 inches anda cell height of about 0.030 inches for a cell area of about 0.0012square inches. As another example, for an expandable tip assemblyconfigured to be inserted into 5 mm vessels and configured to facilitatereperfusion and maceration, the expandable scaffold can have a celllength of about 0.120 inches and a cell height of about 0.050 inches fora cell area of about 0.003 square inches.

As described above, the expandable scaffolds (for example, but notlimited to, expandable scaffold 400, expandable scaffold 500) can havevariable cell sizes along their lengths. In some embodiments, the cellsat the proximal and/or distal end of the expandable scaffold haverelatively small cell sizes and the cells of the central portion of theexpandable scaffold have relatively large cell sizes (e.g., tofacilitate progressive or multiple step therapy).

According to several embodiments, the expandable scaffolds may have aradial geometry. As shown in FIG. 30A, cells 3050 may be defined by aplurality of struts 3060 connected by bridges 3065. As shown in FIG.30A, each strut 3060 may connect at each of its ends at a bridge 3065.Each bridge 3065 may connect three struts. As further shown in FIG. 30A,each open cell 3050 may be defined by six struts 3060, wherein the opencell 3050 is substantially parallelogram-shaped. In some embodiments,each bridge 3065 may connect four struts (for example, as shown in FIGS.27A and 27B).

The cell deformation properties or characteristics can be varied toachieve different therapeutic effects. For example, for flowrestoration, cell deformation can be maximized or increased to minimizeor decrease thrombus penetration into the expandable scaffold, therebyallowing maximum or increased blood flow through the blood vessel. Forthrombus removal, cell deformation can be minimized or decreased to keepthe largest cell shape and cell area open to maximize or increasethrombus penetration or protrusion into the scaffold, thereby enhancingthe likelihood of clot capture and extraction in a single pass. Celldeformation can be affected by multiple factors such as, but not limitedto, cell size, strut widths, strut thicknesses, strut lengths, cellconnection types (e.g., bridges), and material properties.

e. Strut/Bridge Design

In some embodiments, the thickness, width, and/or shape of the strutscan be varied depending on the purposes to be achieved by the expandablescaffolds (e.g., thrombus engagement, thrombus penetration).

According to several embodiments, for a given pressure provided by anexpandable scaffold, a smaller strut width (w) increases the amount ofpressure per unit area applied by the expandable scaffold. Thus, thestruts of the expandable scaffold may more easily cut through a clotwith a smaller strut width. According to several embodiments, a largerstrut width (w) improves channel development through a clot. Where astrut provides a wider width, it displaces a greater amount of clotagainst the walls of the blood vessel. For example, strut width of anexpandable scaffold may be from about 10 to about 100 microns (e.g.,from about 10 microns to about 75 microns, from about 15 microns toabout 65 microns, from about 25 microns to about 100 microns, from about30 microns to about 75 microns, from about 40 microns to about 90microns, from about 50 microns to about 100 microns, from about 10microns to about 80 microns, from about 10 microns to about 50 microns,from about 50 microns to about 60 microns (e.g., about 54 microns), lessthan 10 microns, greater than 100 microns, or overlapping rangesthereof).

According to several embodiments, strut thickness of the expandablescaffolds may be from about 10 microns to about 100 microns (e.g., fromabout 10 microns to about 60 microns, from about 20 microns to about 80microns, from about 25 microns to 75 microns, from about 30 microns toabout 65 microns, from about 40 microns to about 60 microns, oroverlapping ranges thereof).

Traditionally, in many stents and stent-like structures, one goal is toachieve a ratio of strut thickness to strut width of at least 1.4. Suchhigh ratios have been traditionally preferred for sustaining long-termemplacement of the device. In one embodiment, a ratio of 1.4 or greateraides in the performance of the structure by guiding the manner in whichthe struts bend. By providing the struts with more thickness than width,the structure innately “knows” how to bend and load the struts. Withsuch characteristics, the device is easier to manufacture because itimproves shape setting, the device crimps better, and the device isbetter able to resist loading that is normal to diameter.

Because pinching stiffness (k_(p)) is predominantly determined by strutthickness and hoop stiffness (k_(θ)) is predominantly determined bystrut width, a structure with a relatively high ratio of strut thicknessto strut width will provide relatively high pinching stiffness (k_(p)).In other words, given a thickness to width ratio of at least 1.4, thepinching stiffness of the device increases rapidly when greater hoopstiffness are desired. For example, to increase the hoop stiffness at acertain rate to achieve desired hoop stiffness characteristics wouldcause pinching stiffness to increase by at least about double the rateat which the hoop stiffness is increased for ratios exceeding 1.4. Theseincreases in pinching stiffness may result in undesirablecharacteristics of the resulting structure. In contrast, a structurewith a relatively low ratio of strut thickness to strut width willprovide relatively high hoop stiffness (k_(θ)) without yieldingdetrimentally rapid increases in pinching stiffness.

According to several embodiments, the expandable scaffolds of thepresent disclosure may have a strut thickness to strut width ratio ofless than at least about 1.1, 1.2, 1.3, 1.4, or 1.5, etc. For example,the ratio of strut thickness to strut width may be between about 0.4 toabout 1.2. The expandable scaffolds may achieve this strut thickness tostrut width ratio of less than 1.4 due to dimensional constraints. Forexample, the expandable scaffolds may achieve lower ratios where it isapplied for temporary or short-term therapy rather than permanent orlong-term emplacement. In some embodiments, the strut thickness to strutwidth ratio can be greater than 1.4 (e.g., 1.5, 1.6, 1.7, 1.8, 1.9, 2.0,2.1, 2.2, 2.3, 2.4, 2.5).

With reference to FIG. 30B, the expandable scaffolds can comprise cellshaving struts and/or bridges that vary in thickness. FIG. 30Billustrates a representative cell 3050′ of an expandable scaffold havingstruts 3060′ and bridges 3065′ of varying thickness (e.g., dualthickness, step-wise thickness changes or gradually varying thickness).The struts 3060′ vary in thickness along their length, with an increasedthickness at a central portion 3070 of the struts 3060′. The bridges3065′ connecting the struts 3060′ can form X-shaped connections ofvarying thickness (as shown). The varying thickness of the struts 3060′and/or the bridges 3060′ advantageously can impart flexibility,kinkability, or bendability, which improves wall apposition on curvesand bends, and can improve thrombus engagement. For example, the struts3060′ can flex at two or more points (e.g., two, three, four) ratherthan one. In some embodiments, each cell 3050′ of the expandablescaffold flexes independently of each other. Referring back to FIGS. 23and 27A and 27B, for example, the expandable scaffolds can comprisecells having uniform strut thickness. The expandable scaffolds of FIGS.23 and 27A and 27B have relatively smaller nested cells having U-shapedconnections between the cells. In some embodiments, the expandablescaffolds of FIGS. 23 and 27A and 27B allow for substantial celldeformation, which can improve flow restoration.

Turning to FIGS. 31A-31D, the shapes or profiles of the struts can bevaried. For example, the contact surface of the struts can be rounded,squared off (FIG. 31A), pointed (FIG. 31B), or grooved (FIG. 31C) asdesired and/or required for different purposes. The squared off profileor configuration can be used, for example, to enhance the contactsurface area of the expandable scaffold, thereby enhancing compressionof the clot and reperfusion of the vessel. The pointed profile orconfiguration (e.g., sharpened, tapered, wedge-like) can be used, forexample, to enhance penetration of a clot, thereby facilitatingengagement of the clot or maceration of the clot. The grooved profile orconfiguration can be used, for example, to enhance clot engagement andadhesion, thereby improving clot extraction.

FIG. 31D illustrates a strut having a grooved profile that furtherincludes projections or appendages 3145 extending from the grooves toenhance clot engagement and adhesion. The projections or appendages canbe straight, angled, curved, or spiraled. The projections or appendagescan include surface features or a surface finish to improve clotadhesion, such as roughened surfaces, bumps, rims, ridges, holes,cut-outs, recesses, serrations, and/or the like. In some embodiments,the grooved struts comprise ground grooves. The exterior surfaces of thegrooved struts can be ground or roughened (e.g., via sandblasting,oxidation, and/or vapor deposition methods) to improve clot engagementand adhesion. The bridges can comprise flaring bridges. In someembodiments, the bridges include surface finishing such as describedabove (e.g., roughened surfaces formed by sandblasting, oxidation,and/or or vapor deposition methods).

In some embodiments, the exterior contact surfaces of the struts of theexpandable scaffolds can be treated or altered to achieve desiredeffects. For example, the struts can be polished (e.g. using acidcleaning methods) to allow the expandable scaffold to slip across aclot, thereby minimizing or reducing clot adhesion and penetration. Insome embodiments, polished scaffolds can be used for devices configuredto provide effective reperfusion and in-situ clot management (e.g.,lysis and maceration). In some embodiments, the exterior contactsurfaces of the struts are roughened (e.g., using oxidation, vapordeposition, and/or sandblasting methods) to facilitate clot adhesion andclot capture.

f. Expandable Scaffold Profiles

With reference to FIGS. 32A-32F, the expandable scaffolds can comprisevarious profiles, shapes, geometries, or configurations. The profiles,shapes, geometries, or configurations can be selected based on a desiredclinical effect. In some embodiments, the expandable scaffolds have auniform diameter across their length. For example, FIG. 32A illustratesan expandable scaffold 3210A having a cylindrical shape having aconstant diameter. In some embodiments, the expandable scaffolds have avarying diameter. For example, FIG. 32B illustrates an expandablescaffold 3210B having an undulating, or hourglass, shape. In variousembodiments, the expandable scaffolds comprise triangular configurations(FIG. 32C), cross-shaped configurations (FIG. 32D), spiralconfigurations (FIG. 32E), and/or tapered (e.g., funnel-shaped,cone-shaped) configurations (FIG. 32F). The expandable scaffolds canhave a shape or configuration that is generally planar.

V. Use

A. General Use/Indications

The present disclosure relates to revascularization systems and devicesused to treat, among other things, ischemic stroke. Naturally,therefore, the revascularization devices of the present disclosure aredesigned to be used in neuro-type applications, wherein thespecifications of the present catheters and revascularization devicesmay be deployed in the blood vessels of the cerebral vascular system.Similarly contemplated for the revascularization systems and cathetersof the present disclosure is deployment in other parts of the bodywherein the specifications of the present disclosure may be used inother vessels or lumens of the body in a minimally invasive ornon-invasive manner.

The revascularization systems and devices of the present disclosure canbe used for revascularization of blood vessels. When the catheter-basedrevascularization systems of the present disclosure are deployed into ablood vessel having an embolus, a revascularization device, such as anexpandable tip assembly, is expanded, thereby opening the vessel so thatthe vessel can resume proper blood flow. In accordance with someembodiments, once the blood vessel is revascularized, arevascularization device (e.g., an expandable tip assembly) is modifiedto be in a removable state together with filtered detritus, and thecatheter-based revascularization system is removed from the bloodvessels of the patient.

Briefly stated, according to several embodiments a revascularizationdevice (e.g., an expandable tip assembly) is deliverable through highlyconstricted and tortuous vessels, entering a zone associated withsubject emboli, where deployment impacts an embolus, compacting the sameinto luminal walls which enables perfusion and lysis of the embolus,while the revascularization device itself remains continuous with thedelivery system acting as a filter, basket or stand alonerevascularization mechanism, depending on the status of the embolus andother therapeutic aspects of the treatment being offered forconsideration.

According to several embodiments of the present disclosure, clot therapymay have one or more of at least three objectives or effects: macerationof a clot, removal of a clot, and lysis of a clot.

Maceration of a clot refers to the process or result of softening of theclot or breaking the same into pieces mechanically or by using vascularfluids. For example, pressing or compressing the clot with a mechanicalmember can cause the clot to soften, break up or fragment, whereby,exposure of more surface area of the clot (or portions thereof) tovascular flow may cause the clot (or portions thereof) to macerate,soften, or diffuse. In some embodiments, maceration can occur by naturallysis or by unsheathing and resheathing the expandable tip assembly fromthe microcatheter (which may be repeated multiple times if necessary).Maceration can comprise axial maceration, radial maceration or both. Insome embodiments, maceration comprises only axial maceration.

In some embodiments, maceration comprises imploding a clot from withinwithout regard or concern for distal embolization. The lack of concernfor distal embolization can stem from the fact that blood flow has beenreestablished and so any clot fragments that escape downstream willnaturally be lysed without causing any further occlusion.

In accordance with several embodiments, maceration (alone or incombination with natural lysis) of the clot performed by the systems anddevices described herein shaves down, or removes, from 10% to 30% of theclot; however, in some embodiments, more than 30% of the clot can beshaved down, or removed (e.g., 35%, 40%, 50%, 60%, 70%, 80%, 90% or100%) depending on the nature of the clot. Although removal may still berequired even after maceration, the maceration process (in combinationwith lysis) advantageously improves efficacy of clot removal by reducingthe size (e.g., total volume, mass, cross-sectional dimension) of theclot or removing the rubbery soft portions of the clot.

In some embodiments, maceration improves clot extraction because theclot is better formed. For example, maceration can cause a rubbery softportion of the clot comprising platelets and red blood cells to be lysedaway so that only the hard fibrin core remains. In some embodiments, theclot can become easier for an expandable tip assembly to grab andtherefore can make the clot more likely to be removed. Maceration canprevent distal embolization from occurring when removing the clot.

In some embodiments, multiple layer embolus removal is provided due tothe combination of reperfusion, lysis and maceration. For example,reperfusion of the occluded vessel and maceration of the clot canfacilitate an initial lysis or breakdown of the embolus. For example, asdescribed above, the lysis and maceration can remove a soft rubberyouter portion of the embolus. After lysis and maceration, the remaininghard core portion of the embolus can be captured and extracted.

In some embodiments, clot removal can be enhanced or improved bydeployment of adherents or compounds that enhance platelet activation.In some embodiments, the adherents or compounds can be delivered througha lumen of an expandable tip assembly. In other embodiments, theexpandable tip assembly can comprise a coating comprising substancesconfigured to enhance platelet activation or otherwise enhance clotadhesion.

Many of the embodiments described herein are especially advantageousbecause embolic protection devices (e.g., nets, braids, filters,baskets, placed distally or proximally) are not needed. Further,temporarily occluding blood flow (e.g., by a sealing balloon placedproximally or distally) to prevent the flow of emboli is not needed insome embodiments. In some embodiments, the present invention occludesblood flow during removal of the system (e.g., guide catheter,microcatheter), but does not occlude blood flow during treatment.Several embodiments of the invention are contrary to prior teachingsthat blood flow must be occluded while removing a thrombus. Instead,several embodiments enhance blood flow to facilitate the natural lysisof embolic particles. This natural lysis can optionally be supplementedwith artificial thrombolytics and/or maceration. In accordance with someembodiments, besides providing essential blood flow to tissue (andreducing apoptosis), the lack of embolic protection devices or temporaryocclusion devices during treatment aids in visualization of thevasculature, which may be impeded by the use of said devices. In someembodiments, the lack of embolic protection devices (such as filters,baskets, nets, etc.) is advantageous because of the associated risks ofsuch devices. For example, embolic protection devices can be associatedwith deleterious slow flow or no flow due to clogging of the device.

According to several embodiments of the system and processes of theinvention, in certain iterations, once deployed, the expandable tipassembly compacts the embolus against the luminal wall, creating achannel for blood flow which may act like a natural lytic agent to lyseor dissolve the embolus. It is noted that if blood flow does not lysethe blood embolus, natural lysis can be supplemented by the infusion oflytic agents in some embodiments. The lytic agents can be infused, forexample, through a lumen (e.g., guidewire lumen) of the elongate member(e.g., pusher tube) of the expandable tip assembly or through a lumen ofthe microcatheter.

The use of artificial lytic agents or maceration has, in some cases,been discouraged prior to Applicant's discoveries, because it wasthought that such agents or actions may facilitate the release ofembolic particles, which would then cause distal occlusions. However,several embodiments of the present invention are particularlyadvantageous because artificial lytic agents or maceration is used inconjunction with the immediate restoration of blood flow. Thus, forexample, the natural lytic process would lyse any embolic particlesreleased (but not lysed) by the artificial lytic agent or maceration. Inthis manner, the natural lytic process and the artificial lytic agent(or maceration) act in concert or synergistically to treat embolicparticles. In one embodiment, this is particularly beneficial because alower dose of an artificial thrombolytic may be used (because of thesynergistic or additive effects of the natural lytic process), therebyreducing the risks of the thrombolytic (including but not limited tohemorrhage).

Although embolic protection and temporary occlusion are not used in manyembodiments, certain embodiments may be used in conjunction with embolicprotection, temporary occlusion or both.

B. Example Clot Management Process

With reference to FIGS. 33A-33F, an example clot management process fortreating an occluded vessel in the cerebral vasculature is illustrated.FIG. 33A illustrates an occluded vessel 3300 in the cerebral vasculaturehaving a clot 3305. With reference to FIG. 33B, under standardinterventional procedures, a guide catheter 3310 can be introduced intoa patient's vasculature (e.g., via an incision in a femoral artery) andpositioned in a desired vessel in sufficiently close proximity to thecerebral vasculature. In some embodiments, the location of the occludedvessel can be determined using angiography. In some embodiments, aguidewire 3320 is then advanced through the guide catheter 3310 andthrough the clot 3305. In some embodiments, the guidewire 3320 follows apath of least resistance through the clot 3305; however, the guidewire3320 can be configured to traverse the clot 3305 along an edge of thevessel 3300 in an eccentric manner (e.g., to the side of the clot 3305)as shown, for example, in FIGS. 34A and 34B, or substantially throughthe middle of the clot 3305 in a concentric manner (as shown, forexample, in FIG. 33B).

With reference to FIG. 33C, a microcatheter 3315 can then be insertedthrough the guide catheter 3310 and over the guidewire 3320 until thedistal tip of the microcatheter 3315 is distal to the distal end of theclot 3305. In some embodiments, the distal tip of the microcatheter 3315is positioned just distal (e.g., between 0.001 mm and 20 mm, between 0.5mm and 15 mm, between 0.5 mm and 10 mm, between 0.5 mm and 20 mm) to thedistal end of the clot 3305. Distal positioning of the microcatheter canbe confirmed by infusing contrast through the microcatheter.

A particular expandable tip assembly 3325 can then be selected based onthe determined location of the occluded vessel 3300 (e.g., based on sizeof the occluded vessel). With reference to FIG. 35, which illustrates aschematic representation of a portion of the cerebral vasculature 3500,a particular expandable tip assembly can be selected based on averagediameters of the arteries of the cerebral vasculature. For example, theanterior cerebral artery 3575 can have a diameter of between 2.5 mm and3.5 mm. The middle cerebral artery 3580 can have a diameter of between1.5 mm and 3 mm, with the M1 segment having a diameter of between 2.0 mmand 3.0 mm and the M2 segment having a diameter of between 1.5 mm and2.0 mm. The diameter of the internal carotid artery 3585 can be between3 mm and 6 mm at various segments, with the carotid siphon 3590 having adiameter of about 4 mm. The vertebral artery (not shown) can have adiameter that ranges between 3 mm and 4 mm and the basilar artery (notshown) can have a diameter that ranges between 2.5 mm and 4 mm. FIG. 35includes approximate example vessel diameters at various locationswithin the cerebral vasculature. As one example, an expandable tipassembly having a scaffold with an expansion diameter of 3 mm can beselected for use in the middle cerebral artery 3580 because the diameterof the middle cerebral artery 3580 is generally 3 mm or less. The use ofan expandable tip assembly having a scaffold with an expansion diameterof 3 mm can decrease cell deformation of the scaffold, therebyincreasing effectiveness.

Referring back to FIG. 33C, in some embodiments, the expandable tipassembly 3325 is inserted through the microcatheter 3315 and over theguidewire 3320 until the distal end of the expandable tip assembly 3325is lined up with the distal end of the microcatheter 3315, which ispositioned at or near the distal end of the clot 3305. In someembodiments, the microcatheter 3315 comprises a radiopaque marker at itsdistal tip to facilitate confirmation of proper positioning of theexpandable tip assembly 3315 (which also may comprise radiopaque markersat its distal end) with respect to the microcatheter 3315. In someembodiments, the expandable tip assembly 3325 can be sheathed in anintroducer tube (not shown) to preserve sterility during transit andduring loading into the microcatheter 3315; however, the introducer tubecan be removed during the advancement of the expandable tip assembly3325. In some embodiments, the introducer tube comprises a high-densitypolyethylene (HDPE) sheath; however, the introducer tube can compriseone or more other polymeric materials.

With reference to FIGS. 33D and 33E, the microcatheter 3315 is thenwithdrawn or retracted while maintaining the position of the expandabletip assembly 3325, thereby unsheathing the expandable scaffold of theexpandable tip assembly 3325 and deploying it within or against the clot3305. FIG. 33D illustrates partial deployment of the expandable scaffoldof the expandable tip assembly 3325 and FIG. 33E illustrates fulldeployment. The withdrawal or retraction of the microcatheter 3315 canbe performed under fluoroscopic guidance.

In accordance with some embodiments, the expandable scaffold of theexpandable tip assembly 3325 is deployed within or against the clotinstead of distal to the clot to avoid damaging the vessel duringlateral movement of the expandable tip assembly 3325. With reference toFIG. 36, deployment within the clot can prevent overexpansion of asmaller vessel or vessel region distal to the clot. For example, if theclot 3305 is positioned at or near a bifurcation (e.g., an MCA/ACAbifurcation) of an occluded vessel 3500 into two smaller-diameterbranches or vessels 3501,3502, deployment of the expandable tip assembly3325 within the clot 3305 obviates the introduction of the expandabletip assembly 3325 within the smaller diameter vessels 3501,3502, therebyreducing the likelihood of overexpansion of the smaller diameter vessels3501,3502.

Referring back to FIG. 33E, in accordance with some embodiments, theexpandable tip assembly 3315 can be resheathed and repositioned asdesired and/or required. Angiographic assessment can be performed toensure blood flow has been restored after deployment of the expandabletip assembly 3315. Deployment can be maintained for several minutes(e.g., 1 to 3 minutes, 3 to 5 minutes, 5 to 10 minutes, greater than 10minutes, or overlapping ranges thereof) depending on the circumstances.The expandable scaffold of the expandable tip assembly 3325 can beresheathed within the microcatheter 3315 and redeployed one or moretimes to provide further maceration of the clot 3305. In someembodiments, any remaining portions of the clot 3305 that have not beenlysed are impacted, engaged and captured by the expandable scaffold ofthe expandable tip assembly 3325 and removed upon withdrawal of theexpandable tip assembly 3325. For example, in some embodiments, a singleexpandable scaffold can be configured both to impact and compress theclot to immediately restore flow and allow natural lysis and to engageany remaining portions of the clot that are not lysed, as describedabove. In some embodiments, any remaining portions of the clot are atleast partially captured, engaged, or grabbed by the expandable scaffoldon the exterior surface of the expandable scaffold. The microcatheter3315 can then be advanced over the expandable scaffold of the expandabletip assembly 3325 to reconstrain the expandable scaffold and themicrocatheter 3315 together with the expandable tip assembly 3325 can bewithdrawn into the guide catheter 3310 and removed from the body, asshown in FIG. 33F. As such, in some embodiments, the expandable tipassembly 3315 is never implanted, detached, or released into the bloodvessel.

According to some embodiments, if the clot is not fully lysed and/or theclot has not been fully captured by the first expandable tip assembly3325, a second expandable tip assembly configured to facilitate removalof clots can be inserted, deployed, and removed in a manner similar tothat described above. In some embodiments, the guide catheter 3310comprises a balloon that can be inflated during removal of the clot3305. Angiographic assessment can be performed to confirm that the clot3305 has been completely lysed or otherwise removed.

In accordance with some embodiments (e.g., laser cut tube scaffolds),the design of the expandable tip assembly 3325 allows for insertion ofthe expandable tip assembly 3325 within the microcatheter 3315 andwithin the clot 3305 without concern for orientation.

C. Progressive, or Modular, Stroke Therapy Process

As described above, a kit of multiple expandable tip assemblies can beprovided to achieve different effects or purposes in addressing a clot.FIG. 37 illustrates a flow diagram of an embodiment of a progressivestroke therapy process 3700. The progressive stroke therapy process 3700starts at block 3702, wherein a microcatheter is inserted into theneurovasculature. The microcatheter can be inserted into theneurovasculature similar to the manner described above (e.g., via aguide catheter and/or over a guidewire to the site of the embolus).

Reperfusion can then be attempted, for example with a reperfusion device(e.g., an expandable tip assembly configured and designed to facilitateimmediate reperfusion) at block 3704 of FIG. 37. In some embodiments,attempted reperfusion can comprise resheathing and unsheathing thereperfusion device one or more times using the microcatheter to attemptto macerate the thrombus, which can enhance lysis of the thrombus. Afterreperfusion is attempted, the success is determined at decision block3706. For example, a contrast dye can be used to determine the level towhich the occluded vessel is reperfused (e.g., an angiographicassessment). In some embodiments, determination of success can occur atleast ten minutes after introduction of the reperfusion device.

If reperfusion is successful to a desired degree, the stroke therapyprocess 3700 ends at block 3708 and the reperfusion device is recapturedwithin the microcatheter and the reperfusion device and themicrocatheter are removed from the body. If reperfusion is notsuccessful to a desired degree, then an embolus capture device (e.g., anexpandable tip assembly designed and configured to facilitate effectiveclot extraction) can be selected and inserted through the microcatheteras described herein and deployed distal to or within the embolus (block3710). At block 3712, the embolus is captured by the embolus capturedevice. In some embodiments, the embolus capture device (e.g., anexpandable tip assembly designed and configured to facilitate effectiveclot extraction) can be resheathed and unsheathed one or more timesusing the catheter to increase clot adhesion and the likelihood of clotcapture. In some embodiments, one or more adherents, agents, orcompounds can be delivered to promote clot adhesion or plateletactivation, as described above. The stroke therapy process 3700 thenproceeds to block 3714, wherein the embolus capture device, the embolus,and the microcatheter are removed from the body.

VI. Supplementary Modalities

In some embodiments, visualization is provided before, during, or aftertreatment. Visualization can be provided using angiography orfluoroscopy (in conjunction with radiopaque markers). In someembodiments, a visualization member (e.g., a visualization scope) can beinserted through a lumen of an expandable tip assembly, a microcatheter,and/or a guide catheter to provide visualization of a target site withina blood vessel. In some embodiments, the guidewire used for tracking andmaintaining access can comprise a visualization member (e.g., at itsdistal tip). In some embodiments, images can be captured duringtreatment and output to a display for viewing. In some embodiments, thecaptured images can be stored in memory of a computing or storage devicefor documentation purposes. In some embodiments, the visualizationmember can transmit images to the display (e.g., via a wired or wirelessconnection). Visualization can facilitate positioning of the devices andsystems described herein within a vessel, within a clot, and/or withrespect to each other, can confirm blood flow restoration, and/or canconfirm clot removal, for example.

In some embodiments, a suction or aspiration catheter, conduit, or lineis inserted into a lumen of the expandable tip assembly, microcatheter,and/or guide catheter. The suction or aspiration means can be used toperform suctioning or aspiration during maceration and/or clot removal,thereby enhancing the removal of material. In some embodiments, themethods described herein can be performed without suction or aspiration.

In some embodiments, one or more fluids and/or other materials can bedelivered to a target embolic region. In some embodiments, such fluidsand/or other materials are configured to loosen, break up, penetrate,degrade, disperse, dissolve and/or otherwise undermine or affect anocclusion (e.g., clot) within a cerebral vessel. In some embodiments,such fluids and/or other materials can aid in removal of the clot and/oraid in clot adhesion (e.g., by deploying adherents or compoundsconfigured to activate platelets or otherwise promote clot adhesion andpenetration). The fluids or materials can be delivered to the targetembolic region via a lumen of the microcatheter or a lumen of theexpandable tip assembly or by a separate delivery catheter. In someembodiments, the elongate member of the expandable tip assembly cancomprise one or more openings or apertures for delivery of fluids ormaterials to the target embolic region.

In some embodiments, fluids and/or other materials that are selectivelydelivered through a channel or lumen of the expandable tip assembly ormicrocatheter include, without limitation: medicaments, biologicallyactive agents, platelet activation agents, thrombogenic agents, heparin,combinations of the same, and/or the like. Ultraviolet, germicidaland/or antimicrobial treatment may be incorporated in severalembodiments. Therapeutic modalities are included in some embodiments,including but not limited to, radiofrequency, ultrasound, laser,microwave, heat, and cryotherapy, or combinations thereof. In oneembodiment, the therapy is used to effect ablation or lysis. In someembodiments, various devices are used to provide sonication, vibration,radiation, and electrical stimulation, or combinations thereof.

VII. Over-the-Wire and Rapid Exchange Systems

According to some embodiments, the revascularization systems (e.g. clotmanagement systems, stroke treatment systems) can provide maintainedarterial access to the treatment site and provide greater support to thearterial tree by being either over-the-wire (OTW) or rapid exchange (RX)catheter-based systems. In some embodiments, the microcathetersdescribed herein comprise rapid exchange microcatheters. Theover-the-wire systems advantageously can facilitate maintained arterialaccess to treatment sites without compromise to reperfusion of bloodflow. The over-the-wire systems advantageously can be used when multipletreatment devices are used during a treatment procedure to maintainarterial access as one device is removed and another is inserted. Therapid exchange systems advantageously can reduce the profile of themicrocatheter or the expandable tip assembly, and provide enhancedvessel support.

In some embodiments, microcatheters having at least second lumens forvessel stability during removal of emboli and/or in adjunct therapymodes can be used, as described in U.S. application Ser. No. 12/422,105,the entire content of which has been expressly incorporated by referenceabove. The rapid exchange systems can allow and maintain arterial accessto treatment sites, and provide enhanced support to the arterial tree,while working as a rapid exchange system. The rapid exchange feature canenable the embolus to be securely captured and removed by providingsupport within the vessel. The OTW or RX support provided can preventthe proximal vessel from buckling or kinking during tensioning uponembolus removal. Buckling or kinking of the vessel can cause theproximal vessel orifice to ovalize, thereby stripping the embolus from acapture device. Expressly incorporated by reference as if fully setforth herein are U.S. Pat. Nos. 7,018,372; 6,893,417; US 2007/0293846;US 2007/0293821; US 2007/0282306; US 2007/0276325; US 2007/0149949; andUS 2007/0197956.

According to some embodiments, an OTW system comprising an expandablestroke device (e.g., the expandable tip assemblies described herein suchas but not limited to the expandable tip assembly 600) is combined witha rapid exchange system as discussed above. The OTW system may beconfigured to fit within a lumen of the RX system. A guidewire may beconfigured to fit within another lumen of the RX system. Examples ofsuch a guidewire include Traxcess®, Agility®, Transend® or Synchro®brands. In some embodiments, the guidewire is a 0.010″ or 0.014″exchange wire and has a length between 200 cm and 400 cm.

Referring now to FIG. 38, according to several embodiments of thepresent disclosure, guidewire 3801 accesses and crosses a target lesion,providing a pathway for RX microcatheter 3815 having at least twolumens. In some embodiments, the guidewire 3801 may be at leastpartially disposed within a first lumen 3802 of the RX microcatheter3815. As described above, the stroke device 3810 can includeradiographic marking elements 3816 for visualization during placement.

According to several embodiments of the present disclosure, the strokedevice 3810 (e.g., the expandable scaffolds described herein such as,but not limited to, expandable scaffold 810, expandable scaffold 910) isshown in a fully expanded position, whereby it functions consistentlyand safely such that arterial support is maintained by virtue of theguidewire 3801 keeping the arterial tree from mechanical stress, whilerapid flow restoration, embolus removal, clot capture and/or otherprocedures are performed. The stroke device 3810 can be deployed in amanner similar to that described above in connection with the stroketreatment process 3300. In some embodiments, the stroke device 3810 isdelivered over a second guidewire inserted within a second lumen 3803that does not contain the guidewire 3801. Thus, reperfusion isestablished and therapy administered without risks to patients that maybe present with other systems or devices. In some embodiments, theguidewire 3801 is a 0.010″ or 0.014″ guidewire and has a length between100 cm and 300 cm.

According to several embodiments, as shown in FIG. 38, the stroke device3810 may be tethered or otherwise coupled to an elongate delivery member3805 such that, while emplaced at a treatment site within a bloodvessel, it remains accessible via the RX microcatheter 3815 and readilyretrievable therein while maintaining reperfusion of the blood vessel.In one embodiment, the stroke device 3810 may be emplaced on a long-termor permanent basis, or as needed based on the amount and type ofrecanalization prescribed.

According to some embodiments, the stroke device 3810 isself-expandable, such that is may expand substantially radially whenremoved from within the RX microcatheter 3815. In some embodiments,additional therapies may be provided while the stroke device 3810 isfully expanded, for example, through the first lumen 3802 of the RXmicrocatheter 3815. For example, therapeutic agents, lytic agents,adherents to promote clot adhesion, irrigation fluids, suction oraspiration catheters, and/or the like, or combinations thereof can bedelivered through the first lumen 3802 of the RX microcatheter 3815while the stroke device 3810 is deployed within the vessel.

According to several embodiments of the present disclosure, a processfor making a neuro-monorail microcatheter (e.g., the RX microcatheter3815) is disclosed. The process may include cutting a distal segment ofa first tube having a first lumen. The distal segment may be cut atabout 5 cm to 50 cm (e.g., 5 cm to 10 cm, 10 cm to 20 cm, 15 cm to 30cm, 20 cm to 40 cm, 35 cm to 40 cm, or overlapping ranges thereof) froma distal end of the micro first microcatheter. The remaining distalsegment of the first tube may be aligned adjacent to a distal section ofa second tube having a second lumen. In some embodiments, the distalends of the first and second tubes are aligned. Guidewires may be placedin each of the first and second tubes to maintain their respectivealignments and keep their lumens open. A resin, such as PET or PTFE, oran adhesive, heat shrink, sealant, or other surface treatment may beapplied in short segments along the lengths of the first and secondtubes to secure and maintain alignment and adjacent status of thefinished dual-lumen or neuro-monorail microcatheter. The distal segmentof the first tube forms a rapid exchange lumen or port configured toreceive the guidewire 3801.

In accordance with some embodiments of the present disclosure, a firstand second tube, as described above, may be co-extruded together andthen the first tube can be skived or cut to form the distal segmentdescribed above, in lieu of aligning and joining two separate tubes asdescribed above.

VIII. Balloon Catheter Systems

In accordance with some embodiments, the revascularization systems(e.g., stroke treatment systems, clot management systems) compriseballoon catheter and delivery systems. Although described as a separateembodiment of a system, the devices and features described in connectionwith the balloon catheter systems can be used, combined with, orsubstituted for, devices and features of the other systems (e.g.,revascularization system or clot management system 300) describedherein. With reference to FIGS. 39-41, according to several embodimentsof the present disclosure, a balloon catheter and delivery system 3900includes a catheter 3915 and a balloon 3926. The system 3900 may have adistal end 3924 and a proximal end (not shown). FIGS. 39 and 40illustrate the balloon 3926 in its non-inflated and inflatedconfigurations, respectively. FIG. 41 illustrates deployment of anembodiment of an expandable scaffold (e.g., cage-like structure) 3910from the catheter 3915.

With reference to FIG. 42, according to several embodiments of thepresent disclosure, a balloon catheter and delivery system 4210 maycomprise a proximal end 4222, a distal end 4224 and at least one lumen.A catheter 4215 may be of any length for performance of minimallyinvasive vascular treatments. For example, for treatment of stroke,aneurysm, or other treatments within the brain of a patient, a catheter4215 may have a length of between about 135 cm and about 150 cm (e.g.,between about 135 cm and 140 cm, between about 140 cm and 150 cm).However, in some embodiments, the catheter 4215 has a length less than135 cm or greater than 150 cm.

The catheter 4215 may be of variable stiffness that is able to track toand through the tortuous anatomy or the cerebral vasculature (i.e.,internal carotid artery, MCA, ACA, vertebral and basilar). The catheter4215 may be one or two pieces and may have greater proximal pushability(stiffness) and greater distal flexibility (softness) to allow trackingto distal cerebral arteries.

According to several embodiments, there may be provided at least oneballoon 4226 near a distal end 4224 of the catheter 4215 for lumendilatation, treatment of ICAD, vasospasm, flow arrest and remodeling ofaneurysm necks during coiling. According to several embodiments, theballoon 4226 is disposed outside the outer surface of the catheter 4215,such that the catheter 4215 is concentrically disposed within a portionof the balloon 4226, and such that the balloon 4226 expands radiallyaway from the catheter 4215. The balloon 4226 may be a percutaneoustransluminal angioplasty (“PTA”) balloon. In one embodiment, a pluralityof balloons 4226 may be provided on an outer surface of catheter 4215.In one embodiment, the balloon 4226 may have a diameter in an inflatedstate of between about 0.018″ and about 0.035″.

The balloon 4226 may be comprised of materials such as Pebax, nylon,PTFE, polyethylene terephthalate (“PET”), polyurethane, polyester, anelastomeric material, or other suitable materials or mixtures thereof.The balloon 4226 may be of any length that facilitates adequate crossingof an occlusion. For example, the balloon 4226 may be between about 1.5cm and about 6.0 cm in length (e.g., 1.5 cm to 2 cm, 2 cm to 3 cm, 2.5cm to 3.5 cm, 3 cm to 4 cm, 4 cm to 6 cm, or overlapping rangesthereof).

With continued reference to FIG. 42, at least one inflation lumen 4229may provide fluid communication to the balloon 4226 from the proximalend 4222 of the catheter 4215. The inflation lumen 4229 may provide afluid to the inner portion of the balloon 4226, such that the fluidfills and inflates the balloon 4226. The inflation lumen 4229 may beopen at or near the proximal end 4222 of the catheter 3915, and may beconfigured to interface with a luer adaptor, fitting, handle, syringe,injector, plunger, or any other one or more selectable items foroperation of the balloon catheter and delivery system by a user.Likewise, using ePTFE, PTFE, or other lubricious and/or drug elutingelements with the lumens 4228 and/or 4229 is contemplated.

According to several embodiments, an expandable device 4225 (e.g., anyof the expandable tip assemblies described herein) is configured to bedisposable within the delivery lumen 4228. The expandable device 4225may include a tether 4205 (e.g., elongate member) and a cage-likestructure 4210 (e.g., expandable scaffold). Tether 4205 may be attachedto the cage-like structure 4210 and may be selectively detachable.Tether 4205 may extend to or beyond the proximal end 4222 of catheter3915. The expandable device 4225 may be disposable and trackable withinthe delivery lumen 4228 of the catheter 4220.

According to some embodiments, at least a portion of the cage-likestructure 4210 may be tapered at or near a point of attachment with thetether 4205. For example, a design may be provided tapering from thediameter of the tether 4205 to the largest diameter of the cage-likestructure 4210. Likewise, alternate geometric configurations can be used(e.g., everted, scalloped, and other variant ends or edges).

According to several embodiments, the cage-like structure 4210 may bemade of nitinol to allow it to be compressed and loaded into anintroducer for packaging; however, “super-elastic” materials and othermemory-based materials can be used. In one embodiment, the cage-likestructure 4210 is compressible and expandable, such that it maintains acompressed state when within a lumen or sheath and may maintain anexpanded state when outside the lumen. In one embodiment, the cage-likestructure 4210 may be “self-expanding”, such that it expands onceunsheathed from the delivery lumen 4228 of the catheter 4215.

By attaching it to a delivery wire (e.g., tether 4205), in someembodiments, the cage-like structure 4210 can be placed, retracted,repositioned and recaptured into a catheter. These features allow forthe following: 1) perfusion of blood through the artery during coiling;2) perfusion from coiling herniation or prolapse; and 3) removal of thedevice, mitigating the use of Aspirin and Plavix.

According to several embodiments, the delivery lumen 4228 has an innerdiameter sized to accommodate the cage-like structure 4210. According toseveral embodiments, at least one delivery lumen 4228 provides a pathwaythrough the catheter 3915 from about the proximal end 4222 of thecatheter 4215 to about the distal end 4224 of the catheter 4215. Thedelivery lumen 4228 may be open at or near proximal end 4222 of thecatheter 4215, and may be configured to interface with a luer adaptor,fitting, handle, syringe, injector, plunger, or any other one or moreselectable items for operation of the balloon catheter and deliverysystem by a user. As discussed, PTFE, ePTFE and other lubricious and/oreluting elements are incorporated within at least the lumen 28.

In some embodiments, delivery lumen 4228 may be lined withpolytetrafluoroethylene (“PTFE”) or a polymer thereof, alone or incombination with other materials, coatings, coverings, or deliverysurfaces or substrates.

According to several embodiments, the catheter 4220 and the expandabledevice 4225 may be configured to travel together, such that theexpandable device 4225 may selectively accompany the catheter 4215 asthe catheter 3915 travels through or is placed within a vasculature. Forexample, the catheter 4215 and the expandable device 4225 may be jointlydelivered to a location while the cage-like structure 4210 remainswithin delivery lumen 4228.

In several embodiments, the catheter 4215 and the expandable device 4225may be configured to be separately disposable, such that they may bemoved relative to each other. For example, the expandable device 4225may be advanced or retracted relative to the catheter 3915 byadvancement or retraction of only the tether 4205 at the proximal end4222 of the catheter 4215. Likewise, the catheter 4215 may be advancedor retracted relative to the expandable device 4225 by advancement orretraction of only the catheter 4215.

According to some embodiments, the catheter 4215 is configured toprovide tracking over a guidewire (not shown) as described in moredetail herein. One or more lumens of the catheter 4215 may provide apathway for a guidewire using an over-the-wire (OTW) system, asdescribed in more detail herein.

In some embodiments, a method is disclosed for treatment of a vascularocclusion, particularly a neurovascular occlusion. With reference toFIG. 43, according to several embodiments of the present disclosure, theballoon catheter and delivery system 4210 may be provided to anocclusion.

With reference to FIG. 44, according to several embodiments of thepresent disclosure, the balloon catheter and delivery system 4210 maycross the occlusion by leading with the distal end 4224 of catheter3215. Crossing may be effectuated by pressure, force, ablation, orapplication of one of various types of energy at the distal end 4224 ofthe catheter 4215. Crossing may create an initial channel bydisplacement of the occlusion in the presence of the balloon catheterand delivery system 4210.

With reference to FIG. 45, according to several embodiments of thepresent disclosure, the balloon 4226 may be inflated or the catheter4215 may otherwise be dilated. Inflation of the balloon 4226 may furtherdisplace or compress at least a portion of the occlusion away from thecatheter 4215. Thereby, a broader channel may be created by the balloon4226, wherein the diameter or cross sectional area of the channelexceeds the diameter or cross sectional area of the catheter 4215.

With reference to FIG. 46, according to some embodiments of the presentdisclosure, the balloon 4226 is deflated, whereby the broader channelexceeding the size of the catheter 4215 remains open at leasttemporarily.

With reference to FIG. 47, according to several embodiments of thepresent disclosure, the catheter 4215 is withdrawn from an occlusion.The operation of withdrawing the catheter 4215 may simultaneously resultin unsheathing and deployment of the cage-like structure 4210.Deployment of the cage-like structure 4210 may result in an expansion ofany portion of the cage-like structure 4210 that is not within the lumen4228 of the catheter 4215.

With reference to FIG. 48, according to some embodiments of the presentdisclosure, the catheter 4215 may be withdrawn such that the cage-likestructure 4210 may achieve a fully deployed state. For example, a fullydeployed state may be achieved when the entire length of the cage-likestructure 4210 is outside the delivery lumen 4228 of the catheter 4215,or when at least a length of the cage-like structure 4210 correspondingto the length of the occlusion is outside the delivery lumen 4228 of thecatheter 4215. Expansion of the cage-like structure 4210 may maintainthe approximate size and dimensions of the broader channel created bypreviously inflating the balloon 3926.

With reference to FIG. 49, according to several embodiments of thepresent disclosure, the cage-like structure 4210 achieves a temporary orlong-term steady-state fully deployed state, wherein improved flow maybe achieved through the occlusion. The flow through the channel mayfacilitate lysis (e.g., natural lysis) of the occlusion and itsconstituent parts. The cage-like structure 4210 may maintain the channelcreated by the dilation or inflation of the balloon 4226, even as thechannel deforms or is otherwise modified by the improved flow. Accordingto several embodiments, the cage-like structure 4210 may be maintainedwithin the channel of the occlusion.

In some embodiments, the cage-like structure 4210 may be retracted intothe delivery lumen 4228 of the catheter 4215, and the catheter 4215 maybe removed from the location of the occlusion.

IX. Expandable Tip Microcatheter

In accordance with some embodiments, a revascularization system (e.g.,revascularization system 300) can include a microcatheter having anexpandable tip at its distal end. Thus, in some embodiments, instead ofa revascularization system comprising a microcatheter and a separateexpandable tip assembly configured to be inserted through themicrocatheter, the two components can be combined into a singleexpandable tip microcatheter.

In some embodiments, the expandable tip microcatheter operates as amicrocatheter during introduction into a patient. An active segment ofthe expandable tip microcatheter may expand radially to reperfuse, lyse,or macerate emboli, thrombi, clots, occlusion, blockage, or other matterin a vessel (which terms may be used interchangeably according toembodiments of the present disclosure). After reperfusion is achieved,the active segment may be returned to its configuration maintained priorto expansion, and the expandable tip microcatheter may be removed.

According to several embodiments, and as illustrated by an embodiment inFIG. 50, there is shown a microcatheter 5000 with an active segment 5010in an unexpanded state. The microcatheter 5000 comprises a proximalsegment 5002 and a distal segment 5004. The proximal segment 5002 orportions thereof may remain accessible outside of the patient and may beused to insert and retract the microcatheter 5000, as well as to deploythe active segment 5010 during operation. As illustrated by anembodiment in FIG. 51, the active segment 5010 may be deployed to anexpanded state, at least a portion thereof having a radius greater thanin an unexpanded state.

According to several embodiments, the length and diameter of themicrocatheter 5000 are suitable for inserting into a human patient andcapable of reaching a target embolus, for example, in the region abovethe subclavian and common carotid arteries. For example, themicrocatheter 5000 may be about 150 cm long; the proximal segment 102may be about 115 cm with an outer diameter of about 4 F and the distalsegment 104 is about 35 cm with an outer diameter of about 2.7 F. In oneembodiment, the microcatheter 5000 is 135 cm long, proximal segment 1102is 90 cm long, and distal segment 1104 is 45 cm long. In one embodiment,the microcatheter 5000 has an inner diameter of 0.012″. In someembodiments, a gradual decrease (e.g., stepwise, tapered, etc.) in theouter diameter dimension may be provided as a function of the distancealong proximal segment 5002. For example, the proximal segment 5002 maybe 4 F at the most proximal end and the distal segment 5004 may be 2.7 Fat the most distal end. Disposed between may be at least one segmenthaving one or more intermediate outer diameters between 4 F and 2.7 F(e.g., 3.8 F, 3.6 F, 3.4 F, 3.2 F, 3.0 F, etc. (see FIGS. 50, 51, 54,and 55). Microcatheter 5000 may have at least one lumen having an innerdiameter of about 0.007 to about 0.021 inches, which allowsmicrocatheter to be inserted along a preinserted guidewire 5300 or usedto infuse therapeutic agents. According to several embodiments, theperformance of microcatheter 5000 is comparable to variousmicrocatheters and is designed to track over the guidewire 5300 or otherguidance structures through the neurovasculature. Other ranges ofmeasurements, dimensions, or attributes that may be varied based on theneeds and specification of the vasculature.

According to several embodiments, an activation member 5020 (see FIGS.52B and 53B) may be provided to selectably radially expand and retractactive segment 5010. The activation member 5020 may be a structure thatconnects the distal segment 5004 to the proximal segment 5002 or anothercomponent of the microcatheter 5000. According to several embodiments,the activation member 5020, components thereof, devices attachedthereto, or devices capable of acting upon the activation member 5020may be directly accessible by a user, for example, at a proximal end ofthe microcatheter 5000 (via a hub, luer, fitting, etc.). The activationmember 5020 may allow a user of the microcatheter 5000 to deploy theactive segment 5010.

According to several embodiments, the activation member 120 may compriseone or more materials, including stainless steel wire or braid,composites polymers and metal braids, ribbon or wire coils. Asillustrated in FIGS. 52A, 52B, and 52C, the activation member 5020 mayextend through a lumen of the microcatheter 5000. For example, as shownin FIG. 52B, the activation member 5020 may be a wire extending throughat least a portion of the proximal segment 5002. Likewise, the guidewire5300 may be provided in the same or another lumen of the microcatheter5000. By further example, the activation member 5020 may attach to atleast a portion of the distal segment 5004, such that distal or proximaltravel of the activation member 5020 relative to the proximal segment5002 causes corresponding distal or proximal travel of the distalsegment 5004 relative to the proximal segment 5002.

As illustrated in FIGS. 53A, 53B, and 53C, the activation member 5020may have a hollow lumen and extend through a lumen of microcatheter5000. The guidewire 5300 may be disposed within the hollow lumen of theactivation member 5020, as shown in FIG. 53B. The activation member 5020may slidably move over guidewire 5300 to reach the distal segment 5004.Other devices operable during a procedure may be delivered via a hollowlumen of the activation member 5020.

According to several embodiments, the activation member 5020 may be abraid (stainless steel, nitinol, composite, polymer, metal, etc.)structure or a ribbon or wire coil. Accordingly, the activation member5020 may be longitudinally or radially compressible, extendable,distensible, or otherwise responsive to forces applied thereto. Forexample, the activation member 5020 may cause the distal segment 5004 tomove relative to the proximal segment 5002 by causing the activationmember 5020 to compress or extend longitudinally. By further example,the longitudinal compression or extension of the activation member 5020may result in adjustment of the relative position of the proximalsegment 5002 and the distal segment 5004 where the activation member5020 is attached to at least a portion of each of the proximal segment5002 and the distal segment 5004. Another device (e.g., guidewire 5300,etc.) may be provided to the activation member 5020 to effect itscompression, extension, etc. According to several embodiments,deployment of the active segment 5010 may be achieved by shortening ofthe activation member 5020, whereby the distance between the proximalsegment 5002 and the distal segment 5004 is decreased.

According to several embodiments, when the active segment 5010 isexpanded in a vessel, the radial expansion causes a channel to be formedin a thrombus for restored blood flow past the occlusion and therebyreperfuse the vessel. Activation of the active segment 5010 may beaccomplished by mechanical methods, such as with the activation member5020 or by using a liner of the microcatheter 5000. Use of the liner isaccomplished by leaving the liner unfused with active segment 5010, suchthat the liner may be independently operable to deploy the activesegment 5010.

According to several embodiments, the activation member 5020 may befused to the distal-most portion of the active segment 5010 or theproximal-most portion of the distal segment 5004. The activation member5020 may further be fused to the proximal-most portion of the activesegment 5010 or the distal-most portion of the proximal segment 5002.

According to several embodiments, the active segment 5010 and theactivation member 5020 may provide opposing forces. For example, theactive segment 5010 may be heat set into a native configuration in anexpanded state. When the activation member 5020 tensions the activesegment 5010, its state changes from an expanded state into adeliverable state. Such tension may be provided by longitudinalextension of the activation member 5020 or travel thereof, therebycausing the proximal segment 5002 to distance itself from the distalsegment 5004. Once delivered to the site of an embolus, the activationmember 5020 is adjusted to allow the active segment 5010 to relax andthereby expand. Such adjustment may be achieved by shortening thelongitudinal length of the activation member 5020 or travel thereof,thereby causing the proximal segment 5002 to approach the distal segment5004.

By further example, the active segment 5010 may be heat set into anative configuration in an unexpanded state. The activation member 5020may be used to tension active segment 5010 when delivered to the site ofan embolus, thereby expanding it. Such tension may be provided byshortening the longitudinal length of the activation member 5020 ortravel thereof, thereby causing the proximal segment 5002 to approachthe distal segment 5004. Shortening of the activation member 5020 may beachieved in a variety of ways. For example, the activation member 5020may be radially expanded, whereby its longitudinal length is decreased.By further example, the activation member 5020 may be transitioned froma substantially straight shape to serpentine shape, whereby itslongitudinal length is decreased. The guidewire 5300 may act upon orwithin the activation member 5020 to effect such transitions.

Other activation methods include electrical, chemical, and thermalactivators. Hydraulic activation may be accomplished with the activationmember 5020 as a balloon in the interior of the catheter that is filledwith a fluid, thereby expanding the balloon, which expands the activesegment 5010. Fluids, devices, or other materials may be provided toactivation member 5020 to effect a change in the shape, geometry, size,orientation, or position thereof, thereby deploying the active segment5010.

According to several embodiments, the active segment 5010 comprises aradially expandable material. For example, as shown in FIGS. 50, 51, 54and 55, the active segment 5010 may include a woven mesh. A mesh may bemade from materials including polymers, PET, nylon, fluoropolymers,nitinol, stainless steel, vectran, kevlar, or combinations thereof.Other biocompatible materials that may be woven or coiled are similarlycontemplated. The active segment 5010 is, according to severalembodiments, about 5 mm to about 50 mm (e.g., from about 5 mm to about10 mm, from about 10 mm to about 20 mm, from about 15 mm to about 30 mm,from about 20 mm to about 35 mm, from about 30 mm to about 45 mm, fromabout 35 mm to about 50 mm, or overlapping ranges thereof) in lengthwhen expanded and is designed to substantially return to itspre-expansion configuration for removal of the microcatheter 5000 afterreperfusion. In some embodiments, active segment 5010 has an expandeddiameter from 1.5 mm to 3.5 mm and therapeutic lengths of 8 mm, 12 mm,or 16 mm. In one embodiment, active segment 5010 is 15 mm long. [0323]According to several embodiments, the active segment 5010 comprises amesh. The mesh comprises a plurality of individual units, having auniform size or spacing geometry or a variable size or spacing geometry.According to several embodiments where the size or spacing geometry isvariable, smaller size or spacing geometry is used to provide a tightmesh for expanding a channel through the thrombus. Larger size orspacing geometry units allow for increased blood flow through the activesegment 5010. In one embodiment, active segment 5010 comprises a wovenpolymer mesh that is heparin coated. In one embodiment, active segment5010 has a suitable porosity to permit blood flow when expanded. In oneembodiment, releasing expansion of active segment 5010 will trapthrombus in the mesh.

According to several embodiments, as shown in FIG. 55, the activesegment 5010 may comprise both mesh 5010A (e.g., a mesh scaffold) andtethers 5010B. According to several embodiments, the mesh 5010Acomprises an open braid, a covered braid, or other supporting structurewhich may provide at least some porosity. The covering may comprise adistal protection mechanism and may be a polymer, such as polyurethane,or other biocompatible cover materials such as ePTFE or related thinfilm. The tethers 5010B may serve to provide structure and support forthe mesh 5010A, as well as attachment to at least one of the proximalsegment 5002 and the distal segment 5004. Tethers 5010B may furtherprovide openings whereby blood may freely flow from the proximal todistal end of the active segment 5010 through a lumen formed therein.The tethers 5010B may include braids, wires, coils, tangs, and/or othercoupling structures. Materials for the tethers 5010B and mesh 5010A maybe the same, different, or interchangeable, as needed.

According to several embodiments, as shown in FIGS. 56, 57, 58, and 59,the active segment 5010 comprises expandable coiled wires. The coiledwires may be made from stainless steel wire or braid, composite metalpolymers, memory shape alloys (e.g., nitinol), wherein the coil is ableto stably expand and return to an original state. As illustrated in FIG.58, the diameter of the coil may be substantially the same as that ofthe microcatheter 5000 when in a non-expanded state. However, whenexpanded (as illustrated in FIG. 59) the coiled wires expand radiallyaccording to the reperfusion principles disclosed herein. Such radialexpansion may be achieved by a variety of methods, including shorteningof the longitudinal length of the active segment 5010, travel of thedistal segment 5004 relative to the proximal segment 102, rotation ofthe distal segment 5004 relative to the proximal segment 5002. Othermethods include mechanical methods, electrical methods, heat methods,chemical methods, etc., or combinations thereof.

According to several embodiments, as shown in FIGS. 54, 55, 58, and 59,revascularization ports 5012 may provide increased blood flow throughthe lumen of microcatheter 5000, as disclosed further herein. In someembodiments, one or more revascularization ports 5012 can be configuredto delivery fluids or materials to a target treatment site (e.g., lyticagents to a target embolus, platelet activation compounds orclot-promoting adherents).

According to several embodiments, variable cell size or spacing geometrymay be accomplished with points where the braid crosses over fixedfilaments (PICS). Thus, the cell size or spacing geometry varies byvarying the density of the braid. Where high radial force is needed toopen a channel in an embolus, for example, the filaments of the mesh aredenser and therefore cross each other more often, yielding small cellsize or spacing geometry that leads to the application of greater radialforce when the mesh expands. Where reperfusion is desired, the PICS maybe less dense and the resulting cell size or spacing geometry isincreased. Additionally, drug delivery through the microcatheter 5000will be more effective in mesh configurations having a large size orspacing geometry.

The active segment 5010 may be coated or covered with substances, suchas lubricious agents or pharmacologically active agents, according toseveral embodiments. For example, the active segment 5010 may be covered(e.g., coated) with heparin or other agents that are used in clottherapy, such as those that aid in dissolving clots, mitigatingvasospasms, promoting activation of platelets, promoting cell adhesionor engagement.

According to several embodiments, the microcatheter 5000 is designed tofollow a path of least resistance through a thrombus. The guidewire 5300inserted through a thrombus tends to follow the path of least resistancethrough the softest parts of the thrombus. When the microcatheter 5000crosses the thrombus, it likewise follows this path of least resistance.As blood flow is restored, a natural lytic action further helps todegrade (e.g., break up, lyse) the thrombus, as described in more detailherein.

According to similar embodiments, therapeutic agents are deployablethrough the lumen of microcatheter 5000, thereby allowing users ofmicrocatheter 5000 to determine on a case-by-case basis whether toadminister an agent. Active and passive perfusion can thus both beenabled. In some embodiments, the therapeutic agents can be deliveredthrough the revascularization ports 5012. Accordingly, thebraid/geometry of the active segment 5010 is porous to allow the agentto pass from the lumen of the microcatheter 5000 into the blood vesselat the site of an embolus, for example.

According to several embodiments, and as illustrated in FIG. 60A, themicrocatheter 5000 is inserted into a vessel having an occlusion. Aspreviously discussed, the microcatheter 5000 is insertable along theguidewire 5300 through a vessel lumen, according to several embodiments.The microcatheter 5000 penetrates embolus 5210 in the vessel. As shownin FIG. 60B, the active segment 5010 is positioned to coincide with theposition of the embolus 5210. As shown in FIG. 60C, the active segment5010 is expanded, thereby opening a channel in the embolus 5210 andrestoring blood flow. According to several embodiments illustrated inFIGS. 61A, 61B, and 61C, similar principles may be applied where theactive segment 5010 comprises coiled wires.

Once activated, the active segment 5010 allows blood to flow around orthrough the microcatheter 5000 and the active segment 5010 to createtherapeutic benefits associated with reperfusion, as described in detailherein. For example and according to several embodiments, the portionsof the proximal segment 5002 and the distal segment 5004 immediatelyproximal and distal to the active segment 5010 may have a diameter ofabout 2.0 French to about 3.0 French.

According to several embodiments, portions of the proximal segment 5002and the distal segment 5004 may have installed therein revascularizationports 5012, as shown in FIGS. 60A, 60B, 60C, 61A, 61B, and 61C. Therevascularization ports 5012 comprise openings in microcatheter 5000that allow vascular fluids to flow through portions of the microcatheter5000. For example, as shown in FIGS. 60C and 61C, fluid on a proximalside of the embolus 5210 may enter the microcatheter 5000 through atleast one revascularization port 5012 of the proximal segment 5002. Thevascular fluids may travel through portions of the microcatheter 5000,including the active segment 5010, and exit through at least onerevascularization port 5012 of the distal segment 5004. In someembodiments, revascularization ports 5012 provide additional deliverypoints for therapeutic agents or other fluids or materials deliveredthrough the microcatheter 5000.

According to several embodiments, a filter may be placed distal of theactive segment 5010 to prevent embolus pieces detached in thereperfusion process from escaping and causing distal occlusions.Accordingly, the active segment 5010 may be designed to capture piecesof embolus during the reperfusion processes. These pieces are capturedwithin the active segment 5010 when the active segment 5010 is returnedto its initial confirmation after expansion. In other embodiments, afilter is not used.

In some embodiments, the rapid reperfusion device comprises an infusablemicrowire 5050 with an integrated filter 5052 as illustrated in FIG.61D. According to embodiments and as illustrated in FIG. 61E, the rapidreperfusion device comprises an infusable coil 5055. In someembodiments, active segment 5010 is a coil that comprises a largeportion of distal segment 5004, wherein microcatheter 5000 itself coilswhen activated to create a channel through an embolus whereby blood flowis restored.

In some embodiments, the rapid reperfusion device comprises an infusabletemporary stent 5060 as illustrated in FIG. 61F. According toembodiments illustrated by FIG. 61G, an infusable balloon 5065 isconnected to microcatheter 5000 and comprises active segment 5010.Inflation of the infusable balloon 5065 can open a channel through theembolus and begin a lytic process on the embolus (e.g., natural lyticaction due to the restored blood flow or mechanical lytic action).

According to several embodiments, a kit of parts is disclosed. The kitmay comprise components, devices, and systems disclosed herein, as wellas any other compatible with the same, and instructions for use.Likewise, directions for use are included and the device may be part ofa surgical tray or other packaged accessory set for surgeries. The kitmay be a sub-component of a surgical tray.

X. Aneurysm Neck Bridging

In accordance with several embodiments, the systems, devices and methodsdescribed herein (e.g., expandable tip assemblies such as but notlimited to expandable tip assembly 500, expandable tip assembly 600) canbe used to improve or facilitate the treatment of aneurysms. The systemsand devices described herein can be used in a support role with othertherapies. The systems, devices and methods described herein provideongoing revascularization or blood flow while aneurysms are beingmanaged (e.g., by vaso-occlusive coils and/or drug use).

In several embodiments, a method of treating an aneurysm is provided. Inone embodiment, the method comprises identifying a blood vessel havingan aneurysm, inserting an expandable tip assembly into the blood vessel,wherein the expandable tip assembly has a scaffold. The scaffold, whichhas openings (such as pores or cells), is positioned to bridge theaneurysm while permitting blood flow. A microcatheter is insertedthrough at least one opening in the scaffold to deliver coils and/orother fillers into the aneurysm, which inhibits blood flow into theaneurysm, thereby preventing rupture of the aneurysm. The reduction inblood flow typically causes the formation of thrombus in the aneurysm.To the extent that the thrombus releases embolic particles (that mayflow downstream and occlude other vessels), several embodiments areconfigured to facilitate lysis of those embolic particles—in many cases,without the need for a separate embolic protection device.

One type of aneurysm, commonly known as a “wide-neck aneurysm” is knownto present particular difficulty in the placement and retention ofvaso-occlusive coils. Wide-neck aneurysms are herein referred to asaneurysms of vessel walls having a neck or an “entrance zone” from theadjacent vessel, which entrance zone has a diameter of either (1) atleast 80% of the largest diameter of the aneurysm; or (2) is clinicallyobserved to be too wide to effectively retain vaso-occlusive coils. Wideneck aneurysms can refer to aneurysms having a dome to neck ratio lessthan 2:1 or a neck wider than 4 mm.

Vaso-occlusive coils lacking substantial secondary shape strength mayalso be difficult to maintain in position within an aneurysm no matterhow skillfully they are placed. This may also be true of coils that havea secondary shape. For example, a 3D coil that takes a spherical shapemay be herniated out of the aneurysm into the parent vessel if the neckis too wide. Using the systems and devices disclosed herein (e.g.,expandable tip assemblies such as but not limited to expandable tipassembly 500, expandable tip assembly 600) can permit the coils to beheld in the aneurysm until a critical mass of coils is achieved withinthe aneurysm so that the coil mass will not move when the devices arewithdrawn.

In some embodiments, the systems and devices described herein comprise avessel reconstruction system. In some embodiments, the devices disclosedherein (expandable tip assemblies such as but not limited to expandabletip assembly 500, expandable tip assembly 600) are configured formaintaining the vaso-occlusive coils within an aneurysm. In oneembodiment, the device comprises a retainer configured to retain coilswithin the aneurysm cavity. The retainer device (e.g., an expandable tipassembly) can be released into the vessel exterior to the aneurysm. Thedevice can be held in place via the presence of radial pressure on thevessel wall. After the device is released and set in an appropriateplace, a microcatheter can be inserted into the lumen so that the distalend of the microcatheter is inserted into the aneurysm cavity (forexample, through open cells of a scaffold of the device, or expandabletip assembly). One or more vaso-occlusive devices can then be introducedinto the aneurysm cavity. The retainer device can maintain or keep thevaso-occlusive devices within the aneurysm whether it is a large-mouth(e.g., wide-neck) aneurysm or not.

Another approach to filling intracranial aneurysms includes the use ofinjectable fluids or suspensions, such as microfibrillar collagen,various polymeric beads, and/or polyvinyl alcohol foam. These polymericagents may additionally be crosslinked, sometimes in vivo to extend thepersistence of the agent at the vascular site. These agents may beintroduced into the vasculature through any of a variety of knowncatheters. After introduction, the deployed materials form a solidspace-filling mass. Other materials, including polymeric resins,typically cyanoacrylates, hydrogels and other gels, fibrin glues, andcalcium binding seaweed extracts are also employed as injectablevaso-occlusive materials. These materials may be mixed with a radiopaquecontrast material or made radiopaque by the addition of a tantalumpowder. Several embodiments of the invention are used in conjunctionwith said injectable fluids or suspensions, and are particularlyadvantageous because the neck of the aneurysm is reconstructed by theaneurysm neck bridge (e.g., expandable tip assembly), thereby reducinghemodynamic stress to the aneurysm in the flow zone. In someembodiments, the neck of the aneurysm is the target of treatment and notthe aneurysm sac. In accordance with several embodiments, treating theneck of the aneurysm is the solution and not filling the aneurysm withfiller materials. In accordance with several embodiments, if theaneurysm neck bridge (e.g., the expandable tip assemblies describedherein) is able to change or stop the existing flow pattern at the neck,then the aneurysm ceases to grow and the aneurysm is effectivelytreated.

The delivery of liquid filler agents into aneurysms in general can havenumerous obstacles in some cases. The viscosity of the material can makedelivery difficult, and can lead to run on even after the pressure headhas been removed from the delivery catheter. Inadequate opacification ofthe material makes it difficult to see. As a result, the liquid filleragents can leak into the parent vessel, thereby resulting in vesselocclusion and distal embolization into the organ's vascular bed.Generally, these materials can be delivered using an inflated balloonadjacent to the abnormality to be treated. Inflation of the balloonduring delivery leads to temporary vessel occlusion and can result indownstream organ ischemia and even infarction. Several embodiments ofthe invention are used in conjunction with said liquids are particularlyadvantageous because blood flow is not occluded or is occluded for lesstime than would otherwise have been done.

A second microcatheter may be introduced either alongside or through (orboth) an internal lumen of a delivery wire or pushwire delivering aneck-bridge (e.g., expandable scaffold) so as to also permit theintroduction of a filler (also called an embolic agent) into theaneurysm through, around or adjacent the mesh of the scaffold, which mayhave opened spaces or cells that permit the microcatheter and/ordelivery wire to introduce the filler into the aneurysm. Such an agentmay be comprised of metallic or plastic coils, a combination of plasticand metal braid or composite plastic and metal braid, liquid orpolymerized polymeric agents, and/or biologic components of blood andplasma-like thrombin, fibrin or any biologic materials like DNA, RNAplasmids or the like, to fill the aneurysm.

However, after, or perhaps during, delivery of a coil (or other filler)into the aneurysm, there may be a risk that a portion of the coil mightmigrate out of the aneurysm entrance zone and into the feeding vessel.This can be especially true in aneurysms where the diameter of theaneurysm neck approaches the diameter of the aneurysm dome in a 1:1ratio. The presence of such a coil in that feeding vessel may cause theundesirable response of forming an occlusion there. Also, there is aquantifiable risk that the blood flow in the vessel and the aneurysm mayinduce movement of the coil farther out of the aneurysm, resulting in amore thoroughly developed embolus in the patent vessel. Being that coilsare constructed from very low gauge wire, the coil mass can compact,resulting in aneurysm recanalization. Thus, in some embodiments, it canbe advantageous to consider needs that can be addressed for aneurysms inlight of the need for ongoing perfusion.

For example, when detachable coils are used to occlude an aneurysm whichdoes not have a well-defined neck region, the detachable coils canmigrate out of the sac of the aneurysm and into the parent artery. Itcan be difficult to gauge exactly how full the sac of the aneurysm iswhen detachable coils are being placed. Therefore, there is a risk ofoverfilling the aneurysm, in which case the detachable coils can alsoherniate or prolapse into the parent artery.

Another disadvantage of detachable coils involves coil compaction overtime. After filling the aneurysm, there remains space between the coils.Continued hemodynamic forces from the circulation act to compact thecoil mass resulting in a cavity in the aneurysm neck. Thus, the aneurysmcan reform over time.

Migration of the filler (sometimes called an embolic agent) may also bea problem. For instance, where a liquid polymer is placed into the sacof the aneurysm, it can migrate out of the sac of the aneurysm due tothe hemodynamics of the system, which can lead to irreversible occlusionof the parent vessel. Several embodiments of the invention are used inconjunction with coils and other types of fillers, and are particularlyadvantageous because the cell size of the scaffold of the aneurysm neckbridge (e.g., the expandable tip assemblies described herein) can sealthe neck to vessel interface, thereby preventing the fillers (e.g.,liquid or solid fillers) from leaking or otherwise exiting from theaneurysm).

In some embodiments, a device is provided that can reconstruct thevessel wall at the aneurysm neck origin by tethering an expandablescaffold (e.g., a cage-like structure or stent-like structure) to thedistal end of a trackable delivery system. For example, an expandablescaffold such as those described herein (e.g., expandable scaffold 810,expandable scaffold 910) can be placed across the neck of aneurysmwithout prophylactically administered aspirin and clopidogrel becausethe device is temporary, as well as without obstructing flow. Thetethered expandable scaffold allows perfusion through the body of thescaffold and provides support to the neck of the aneurysm, therebyallowing a coil procedure. After the coil procedure, the tetheredexpandable scaffold can be withdrawn proximally into a standard deliverymicrocatheter (e.g., microcatheter 315, microcatheter 3315).

The vessel wall reconstruction device (e.g., expandable tip assemblysuch as, but not limited to, expandable tip assembly 600) can bedelivered through standard microcatheters currently available to theinterventionalist. A microcatheter can either be placed into theaneurysm prior to placement of the tethered expandable scaffold or afterplacement of the tethered expandable scaffold. If the latter ispreferred, then the coil microcatheter can be placed through theopenings between struts of the tethered expandable scaffold to accessthe body of the aneurysm to commence coiling.

Referring now to FIG. 62, a delivery tube 6215 deploys a tetheredexpandable scaffold 6210 (e.g., cage-like device, stent-like device suchas, but not limited to, expandable scaffold 610, expandable scaffold810, expandable scaffold 910) prior to insertion of the coil(s) (orother filler), using a standard over-the-wire (OTW) system includingguide-wire 6220. The tethered expandable scaffold 6210 can include thestructure or features of any of the expandable scaffolds describedherein. The delivery tube 6215 and the tethered expandable scaffold 6210can together form an expandable tip assembly (such as but not limited toexpandable tip assembly 510, expandable tip assembly 610). The deliverytube 6215 and the tethered expandable scaffold 6210 can comprise avessel reconstruction system that is able to be deployed prior tofilling, be used to reconstruct the arterial wall at the aneurysm neck,hold filler in place, and then is able to be removed after filling ofthe aneurysm sac is complete.

The vessel reconstruction system (e.g., clot management system,revascularization system) can provide a method to assist in aneurysmfilling that does not restrict blood flow and can be used withoutplacing patients on an anti-clotting drug (including but not limited toacetylsalicylic acid (e.g., aspirin), clopidogrel (e.g., Plavix®) duringfilling of the aneurysm.

According to several embodiments of the invention, the vesselreconstruction system uses both passive and active reperfusion toaddress aneurysms without the detriments of balloon re-modeling. Atemporary tethered expandable scaffold 6210 (e.g., cage-like structure)is non-detachable in some embodiments but attached either to a hypotubeor guide-wire allowing it to be navigated into tortuous vasculature inthe brain. The device and system are deployed prior to filling, asdiscussed above. The expandable scaffold 6210 may be attached toguidewire 6220 or tube 6215.

Referring also to FIG. 63 through FIG. 65, the microcatheter or deliverytube 6215 emplaces the expandable scaffold 6210 at an aneurysm neck,while a coiling microcatheter 6203 accesses the aneurysm, and allows oneor more coils 6207 to be placed therein. The delivery tube 6215 and theexpandable scaffold 6210 may include nitinol or the like “super-elastic”materials.

FIG. 64 likewise provides further details of the vessel reconstructionsystem, with the expandable scaffold 6210 being released from thedelivery tube 6215 using known OTW techniques. In some embodiments, adetachable aneurysm neck bridging system includes a detachable couplingmember 6209 that enables detachment of the expandable scaffold 6210 fromthe delivery tube 6215 for permanent or long-term implantation of theexpandable scaffold 6210.

FIG. 65 and FIG. 66 likewise show intermediate steps, whereby placementof the vessel reconstruction system allows an aneurysm to be isolated,at the neck, whereby the coils 6207 may be used. According to severalembodiments illustrated by FIG. 66, if one of the coils 6207 somehowgets caught in the expandable scaffold 6210, it may be impossible toremove the device without causing damage to or rupturing the vessels.Therefore, according to several embodiments, the expandable scaffold6210 may be detachable, enabling it to be left in the vessel in theevent of a complication where it cannot be safely removed, or as neededotherwise.

The delivery tube 6215 should also have a lumen that enables trackingover a guidewire (e.g., the guidewire 6220). This feature provides a fewbenefits; ability to track and be delivered; ability to maintain accessin the event different size devices need to be exchanged; providesupport to arterial tree during device deployment and recovery. Aflexible device may tend to herniate or prolapse into openings. Theguidewire provides a pathway (concentric) to the artery and supports thedevice preventing such technical complications. The delivery tube 6215can comprise any of the elongate members, microcatheters, or cathetersand the associated features as described herein.

The delivery tube 6215 can be mechanically attached to the expandablescaffold 6210 (e.g., cage-like structure) by soldering, welding or pressfitting or other suitable attachment methods. In some embodiments, thedelivery tube 6215 is attached to the expandable scaffold 6210 via thedetachable coupling member 6209. By attaching the expandable scaffold6210 to the delivery tube 6215, the expandable scaffold 6210 can beplaced, retracted, repositioned and recaptured into a microcatheter. Insome embodiments, the vessel reconstruction system formed by thedelivery tube 6215 and the expandable scaffold 6210 can be deliveredthrough a separate microcatheter. In other embodiments, the expandablescaffold 6210 is attached to a delivery wire to form an expandable tipassembly and the expandable tip assembly can be inserted within thedelivery tube 6215.

The expandable scaffold 6210, being temporary, allows for thefollowing: 1) perfusion of blood through artery during coiling; 2)perfusion from coiling herniation or prolapse; and 3) removal of thedevice, mitigating the use of Aspirin and Plavix.

The expandable scaffold 6210 (e.g., cage-like structure) can be made ofnitinol or other memory-based or shape memory materials to allow it tobe compressed and loaded into an introducer for packaging. Theintroducer enables the device to be transferred into a microcatheter anddeployed to a trusted (e.g., target) location such as an aneurysm neck.

In some embodiments, the expandable scaffold 6210 can comprise alloyscontaining at least 1.5% (wt) and up to about 85% (wt) or more, of oneor more alloying members selected from the group consisting of one ormore of: vanadium, chromium, manganese, iron, and cobalt. U.S. Pat. No.3,351,463 and U.S. Pat. No. 3,753,700 are incorporated by referenceherein.

EXAMPLES

The following Examples illustrate some embodiments of the invention andare not intended in any way to limit the scope of the disclosure.Moreover, the methods and procedures described in the followingexamples, and in the above disclosure, need not be performed in thesequence presented.

Example 1 Stress Test Evaluation for Vessel Tolerance ofRevascularization System with Multiple Device Use

A study was performed to demonstrate that embodiments of multiplerevascularization system devices (e.g., expandable tip assemblies) canbe challenged and delivered to the target vessel, deployed and thenwithdrawn from the target vessel in serial fashion without inducingvessel trauma or injury. Angiographic assessment of the target vesselswas performed after each device deployment and retrieval to assessperformance and outcomes.

Testing was performed on swine animal models. The swine models wereselected because the vascular anatomy and pathological response iscomparable to that of the human. Specifically, the internal maxillaryand renal arteries are of similar diameter to the human middle cerebraland basilar arteries with diameters of 2.5-3.0 mm respectively. Swinemodels have been used by neurovascular companies in support of U.S. FDAIDE studies and/or for 510(k) clearance. Two swine were used in thestudy. The animals were quarantined and examined by qualified veterinarystaff to ensure that they were in good clinical condition. The deviceswere deployed within the inferior and superior renal arteries and theinternal maxillary arteries

In accordance with one embodiment, the testing procedure was performedas follows:

-   -   1. As this was an acute study the animals were sedated,        anesthetized, prepped and draped for a clean but not necessarily        aseptic procedure. Animals were weighed prior to leaving the        prep area. The animal was placed in dorsal recumbency and the        hair removed from the access area (inguinal area).    -   2. Blood was drawn for a baseline activated clotting time (ACT).        Heparin 100-200 IU/kg, IV, was administered to achieve a target        ACT of ≧250 seconds. ACTs were periodically measured in order to        maintain a target ACT of ≧250 seconds. Heparin boluses were        administered as needed in order to achieve this target.    -   3. The femoral artery was accessed via surgical cutdown. A 6 Fr        Cook® introducer sheath was placed in the vessel followed by        placement of a 6 Fr Envoy® guide catheter.    -   4. A Renegade® Hi-Flow™ Microcatheter was inserted into the        guide catheter and the target vessel cannulated.    -   5. Baseline angiographic assessment of the targeted vessel was        performed and vessel diameter measurements obtained and        recorded.    -   6. The rotating hemostasis valve (RHV) on the microcatheter was        loosened and the test device was inserted and advanced to the        target vessel as indicated below.    -   7. Angiography was performed to verify the position of the        device within the target vessel. The device was deployed and        then the Microcatheter and deployed device were retracted back        into the guide catheter (simulated thrombectomy) while applying        syringe aspiration to the guide catheter.    -   8. Post procedure angiography was performed with each device        deployment to assess the target vessel for visible evidence of        trauma, injury or dissection. If evidence of severe vasospasm        was noted 5 mg of Verapamil was administered to relieve the        spasm.    -   9. The next device in the test sequence was then introduced        within the target vessel and steps 6-8 repeated.    -   10. Upon completion of the test sequence the device,        microcatheter and guide catheter were removed from the animal.

The following attributes were assessed: movement of the devices throughthe microcatheter, tracking through the vessel, guidewire movementthrough the system, device deployment, radiopacity, recapture (e.g.,resheathing), withdrawal, thrombectomy, vessel dissection orperforation, and embolization post-treatment. The tested devicesreceived performed as intended ratings for all the above-listedattributes. Vessel response, as evidenced by intra-proceduralangiographic assessment, was similar for all devices evaluated with noangiographic evidence of vessel trauma or injury. Thus according toseveral embodiments of the invention, devices disclosed herein are asafe means of restoring flow in blocked arteries without causing majorlesions or defects such as intramural dissection or perforation oftarget vessels.

Example 2 Usability, Safety and Effectiveness of Expandable TipAssemblies

A study was performed to determine the usability, safety andeffectiveness of embodiments of neurothrombectomy devices comprisingexpandable tip assemblies designed and configured to facilitate clotremoval. Testing was performed on swine animal models. The swine modelswere selected because the vascular anatomy and pathological response iscomparable to that of the human. Swine models have been used byneurovascular companies in support of U.S. FDA IDE studies and/or for510(k) clearance. A total of two subject animals and six blood vesselswere treated. The blood vessels treated were the left and rightascending pharyngeal, lingual and internal maxillary arteries.

Embodiments of the expandable tip assemblies or devices were introducedinto the target vessels, deployed, pulled through the vessels andretracted into the guide catheter in a manner similar to that describedabove. This process was repeated up to six times or until the vessel wasno longer accessible.

The following attributes were assessed: movement of the devices throughthe microcatheter, tracking through the vessel, guidewire movementthrough the system, device deployment, radiopacity, recapture (e.g.,resheathing), withdrawal, thrombectomy, vessel dissection orperforation, and embolization post-treatment. The tested devicesreceived “performed as intended” ratings for all of the above-listedattributes. Thus, several embodiments of the expandable tip assembliescaused minimal disruption or activation of the endothelium (e.g., lessthan 1% endothelial loss, less than 5% endothelial loss, less than 10%endothelial loss).

Example 3 Radial Force and Cell Characteristics Measurements

Testing was performed to compare radial force and cell characteristicsof various vascular therapy devices, including embodiments of theexpandable tip assemblies described herein. The vascular therapy devicestested and/or measured included a NeuroForm³™ device provided by BostonScientific, an IRIIS™ Plus device provided by MindFrame, an IRIIS™device provided by MindFrame, a Solitaire™ AB device provided by ev3,and an Enterprise™ device provided by Cordis. The IRIIS™ Plus and theIRIIS™ devices are embodiments of the expandable tip assembliesdescribed herein.

The following tables illustrate the data collected from the testing.Graphical results of the data from Tables 1 and 2 can be found in FIGS.6 and 7, respectively, of U.S. Patent Application Publication No.2010/0174309, the entire contents of which has been incorporated byreference herein.

Table 1 below lists the data obtained from testing performed todetermine the chronic outward force (COF) of the devices at selectedexpansion diameters ranging from 2 mm to 4.5 mm (which diameterscorrespond to the vessel diameters of the cerebral vasculature). Theunits for the COF data reproduced below are force per unit length(N/mm).

TABLE 1 Diameter NeuroForm³ ™ IRIIS ™ Plus IRIIS ™ Solitaire ™ ABEnterprise ™ 2.0 mm 0.01130 0.0090 0.00590 0.00700 0.00517 2.5 mm0.00950 0.0066 0.00340 0.00410 0.00320 3.0 mm 0.00870 0.0061 0.002550.00210 0.00068 3.5 mm 0.00710 0.0056 0.00255 0.00090 0.00000 4.0 mm0.00460 0.0045 0.00185 0.00000 0.00000 4.5 mm 0.00230 0.0038 0.001650.00000 0.00000

Table 2 below lists the data obtained from testing performed todetermine the radial resistive force (RRF) of the devices at selectedexpansion diameters ranging from 2 mm to 4.5 mm. The units for the RRFdata reproduced below are force per unit length (N/mm).

TABLE 2 Solitaire ™ Diameter NeuroForm³ ™ IRIIS ™ Plus IRIIS ™ ABEnterprise ™ 1.5 mm 0.022 0.016 0.014 0.018 0.005 2.0 mm 0.019 0.0160.011 0.014 0.005 2.5 mm 0.018 0.014 0.009 0.011 0.005 3.0 mm 0.0160.014 0.009 0.008 0.005 3.5 mm 0.014 0.014 0.009 0.005 0.004 4.0 mm0.010 0.012 0.008 0.002 0.003 4.5 mm 0.006 0.007 0.005 0.000 0.001

Table 3 below lists the average COF and RRF of each of the devices asdetermined from the testing results.

TABLE 3 IRIIS ™ Solitaire ™ NeuroForm³ ™ Plus IRIIS ™ AB Enterprise ™Average COF per unit 0.0073 0.0059 0.0030 0.0023 0.0015 length (N/mm)(across 2.0 mm to 4.5 mm diameter) Average RRF per unit 0.0138 0.01270.0083 0.0067 0.037 length (N/mm) (across 2.0 mm to 4.5 mm diameter)

Table 4 below provides a comparison of the strut thickness, cell size,and cell area of various vascular devices. The vascular devices includethe five devices included in the testing described above with respect toTables 1-3, as well as a MindFrame IRIIS™ Large Cell device.

TABLE 4 IRIIS ™ Solitaire ™ IRIIS ™ NeuroForm³ ™ Plus IRIIS ™ ABEnterprise ™ Large Cell Strut 0.0065″ 0.0024″ 0.0027″ 0.0035″ 0.0027″0.0024″ Thickness (inches) Cell Size 0.200″ × 0.070″ 0.120″ × 0.050″0.120″ × 0.050″ 0.230″ × 0.200″ 0.100″ × 0.050″ 0.250″ × 0.100″ (inches)Cell Area 0.007 0.003 0.003 0.023 0.0025 0.0250 (sq. inches)

Example 4 Performance Measurements

Table 5 below summarizes the average performance measurements obtainedfrom published studies of various ischemic stroke treatment devices.Embodiments of the systems, methods and devices described herein wereused in the EU-PRIISM-01 study and the Karolinska University Hospital(PRIISM Subgroup) studies. As shown in Table 5 below, the embodiments ofthe systems, methods and devices described herein resulted in muchfaster “time to flow” results and overall flow results than the systems,methods and devices used in the other studies.

TABLE 5 Study Penumbra Baseline EU- Karolinska ev3 Concentric AspirationInfo/ PRIISM- (PRIISM Solitaire FR Merci International Endpoints 01Subgroup) (Barcelona) US Registry ‘POST’ Number of 35 23 20 164 157Patients Baseline 16.4 16.7 19 16 19 NIHSSS Groin to Initial 26.5 20.5NR 96 41 Flow (min) Groin to final 34.6 33.4   80.9 96 41 flow (min)TIMI II/III on 96.8 90 80 0 0 1^(st) deployment (%) TIMI II/III at 96.895 90 68.3 87 procedure end (%) mRs ≦2 at 90 51.6 60 45 36 41 Days (%)Device related 0 0  0 2.4 3.9 SAE's (%) SICH (%) 2.9 0 10 9.8 6.4Mortality at 90 17.1 10 20 34.0 20.0 days (%)

Conditional language, for example, among others, “can,” “could,”“might,” or “may,” unless specifically stated otherwise, or otherwiseunderstood within the context as used, is generally intended to conveythat certain embodiments include, while other embodiments do notinclude, certain features, elements and/or steps.

Although certain embodiments and examples have been described herein,aspects of the methods and devices shown and described in the presentdisclosure may be differently combined and/or modified to form stillfurther embodiments. Additionally, it will be recognized that themethods described herein may be practiced using any device suitable forperforming the recited steps. Some embodiments have been described inconnection with the accompanying drawings. However, it should beunderstood that the figures are not drawn to scale. Distances, angles,etc. are merely illustrative and do not necessarily bear an exactrelationship to actual dimensions and layout of the devices illustrated.Components can be added, removed, and/or rearranged. Further, thedisclosure herein of any particular feature, aspect, method, property,characteristic, quality, attribute, element, or the like in connectionwith various embodiments can be used in all other embodiments set forthherein.

For purposes of this disclosure, certain aspects, advantages, and novelfeatures of the inventions are described herein. Embodiments embodied orcarried out in a manner may achieve one advantage or group of advantagesas taught herein without necessarily achieving other advantages. Theheadings used herein are merely provided to enhance readability and arenot intended to limit the scope of the embodiments disclosed in aparticular section to the features or elements disclosed in thatsection. The features or elements from one embodiment of the disclosurecan be employed by other embodiments of the disclosure. For example,features described in one figure may be used in conjunction withembodiments illustrated in other figures.

What is claimed is:
 1. An expandable tip assembly adapted to address anocclusive thrombus within a blood vessel without distal embolicprotection, comprising: a variable-stiffness hypotube having a proximalportion, a distal portion and a lumen sized and adapted to receive aguidewire; wherein the distal portion of the hypotube has a greaterflexibility than the proximal portion; wherein the greater flexibilityis provided by spiral laser cuts spaced along the distal portion of thehypotube; wherein the spacing between the spiral cuts decreases from aproximal end of the distal portion to a distal end of the distalportion; an expandable and reconstrainable scaffold coupled to thedistal end of the hypotube, the scaffold being adapted to radiallyself-expand from a non-expanded configuration to an expandedconfiguration upon unsheathing of the scaffold and to transition fromthe expanded configuration to the non-expanded configuration uponre-sheathing of the scaffold; wherein the scaffold comprises a generallycylindrical configuration; wherein the scaffold comprises a laser-cuttube; wherein the scaffold comprises an open distal end without a distalembolic protection member or device; wherein a proximal end of thescaffold comprises a cut-out section adapted to facilitate re-sheathingof the scaffold; wherein the scaffold comprises a plurality of opencells defined by struts and connected by bridges; wherein each strut hastwo ends, with each end connected to one of the bridges; wherein thescaffold has a chronic outward force (COF) per unit length that does notdecrease by more than 75% from an expansion diameter of 1.5 mm to anexpansion diameter of 4.5 mm; and wherein the open cells are sized topromote at least one of vessel reperfusion or thrombus removal.
 2. Theexpandable tip assembly of claim 1, wherein each bridge is connected tofour struts.
 3. The expandable tip assembly of claim 1, wherein thescaffold is coupled to the distal end of the hypotube by a plurality oftether lines that extend eccentrically from one half of the distal endof the hypotube.
 4. The expandable tip assembly of claim 1, wherein thescaffold has a chronic outward force (COF) per unit length that does notdecrease by more than 50% from a diameter of 1.5 mm to a diameter of 4.5mm.
 5. The expandable tip assembly of claim 1, wherein the cells of thescaffold have a uniform cell size.
 6. The expandable tip assembly ofclaim 1, wherein the cells of the scaffold have a variable cell size. 7.The expandable tip assembly of claim 1, wherein the strut thickness issubstantially equal to the strut width.
 8. The expandable tip assemblyof claim 1, wherein the expandable tip assembly comprises a reperfusiondevice and wherein the cells of the scaffold have a cell size adapted toinhibit protrusion of portions of the thrombus within an interior of thescaffold.
 9. The expandable tip assembly of claim 1, wherein theexpandable tip assembly comprises a thrombus removal device, and whereinthe cells of the scaffold have a cell size adapted to promote protrusionof portions of the thrombus within an interior of the scaffold.
 10. Theexpandable tip assembly of claim 1, wherein the cells of the scaffoldhave a cell length of between 4 mm and 6 mm and a cell height between 2mm and 4 mm in the expanded configuration.
 11. The expandable tipassembly of claim 1, wherein the scaffold has an average chronic outwardforce across a diameter of 1.5 mm to 4.5 mm of between 0.0020 N and0.0090 N.
 12. The expandable tip assembly of claim 1, wherein the strutscomprise one or more surface features adapted to enhance engagement ofthrombus material.
 13. The expandable tip assembly of claim 12, whereinthe surface features comprise one or more grooves or one or moreprotrusions or projections.
 14. The expandable tip assembly of claim 1,wherein a central portion of each strut of the scaffold has a greaterthickness than adjacent portions of the strut.
 15. The expandable tipassembly of claim 1, wherein the struts comprise multiple flex pointsalong the length of the struts.
 16. The expandable tip assembly of claim1, wherein the bridges form X-shaped connections between the cells ofthe scaffold.
 17. The expandable tip assembly of claim 1, wherein thebridges have a greater thickness than adjacent portions of the strutsconnected to the bridges.
 18. The expandable tip assembly of claim 1,wherein the scaffold is eccentrically coupled to the distal end of thehypotube with a plurality of tether lines.
 19. The expandable tipassembly of claim 1, wherein the scaffold is permanently, non-removablycoupled to the hypotube.
 20. The expandable tip assembly of claim 1,wherein the scaffold is detachably coupled to the hypotube.
 21. Theexpandable tip assembly of claim 1, wherein the proximal end of thescaffold is open and/or tapered to facilitate resheathing into an outercatheter and increase blood flow through the scaffold.
 22. Theexpandable tip assembly of claim 1, wherein the scaffold has a maximumexpansion diameter of about 1 mm to about 5 mm.
 23. The expandable tipassembly of claim 1, wherein the scaffold has a length of about fromabout 5 mm to about 50 mm.
 24. The expandable tip assembly of claim 1,wherein the scaffold comprises one or more of the following features: atapered body; a coating configured to increase platelet activation oradhesion of the thrombus to the scaffold; a length configured to atleast partially span the thrombus; sufficient radial force to providecontinuous radial expansion as the thrombus is lysed; does not comprisea backbone; and is not a rolled mesh scaffold that is configured tooverlap on itself.
 25. The expandable tip assembly of claim 1, whereinthe scaffold comprises one or more of the following features: a bodyhaving a triangular, elliptical, spiral or undulating configuration; anon-thrombogenic coating or a coating with an anti-clotting drug; aratio of strut thickness to strut width is less than at least about 1.4;parallelogram-shaped cells; and U-shaped bridges between cells of thescaffold.